CA2924318C — Crystalline solvates and complexes of (1s)-1,5-anhydro-1-c-(3-((phenyl)methyl)phenyl)-d-glucitol derivatives with amino acids as sglt2 inhibitors for the treatment of diabetes

USPTO Abstract

What is claimed is: 1. A crystalline structure of a compound of formula I which is (R)-PG (form SD-3), EtOH (form SA-1), ethylene glycol (EG) structure (form SB-1), ethylene glycol (EG) structure (form SB-2), 1:2 L-proline structure (form 3), 1:1 L-proline structure (form 6), or 1:1 L-proline hemihydrate structure (form H.5-2). 2. The crystalline structure as defined in Claim 1 wherein each of said structures is in substantially pure form. 3. The crystalline structure (R)-PG (form SD-3) as defined in Claim 1 having the formula lb characterized by one or more of the following: a) a powder x-ray diffraction pattern comprising 2.THETA. values (CuK.alpha..lambda. = 1.5418 .ANG.) selected from the group consisting of 3.9 ~ 0.1, 8.0 ~ 0.1, 8.7 ~ 0.1, 15.3 ~ 0.1, 15.6 ~ 0.1, 17.2 ~ 0.1, 19.2 ~ 0.1, 19.9 ~ 0.1 and 20.3 ~ 0.1, at room temperature; b) a solid state 13CNMR spectrum having substantially similar peak positions at 15.8, 17.6, 39.0, 60.9, 63.2, 67.4, 69.7, 77.3, 79.2, 79.8, 113.3, 123.6, 129.0, 130.4, 132.0, 135.6, 139.2 and 157.9 ppm, as determined on a 400MHz spectrometer relative to TMS at zero; c) a differential scanning calorimetry thermogram having an endotherm in the range of about 43°C to 60°C or as shown in Figure 8; or -102- d) thermal gravimetric analysis curve with about 18.7% weight loss from about room temperature up to about 235°C or as shown in Figure 6. 4. The crystalline structure EtOH (form SA-1) having the formula lc: characterized by one or more of the unit cell parameters substantially equal to the following: Cell dimensions: a = 11.519(1) .ANG. b = 4.799(1) .ANG. c = 22.648(1).ANG. .alpha. = - degrees .beta. = 94.58(1) degrees .gamma. = - degrees Space group = P2 1 Molecules/asymmetric unit 1 wherein measurement of said crystalline structure is at -50°C and which is characterized by fractional atomic coordinates substantially as listed in Table 6. 5. The crystalline structure EG (form SB-1) having the formula ld: characterized by one or more unit cell parameters substantially equal to the following: Cell dimensions: a = 11.593(8) .ANG. -103- b = 4.766(5) .ANG. c = 22.78(3) .ANG. .alpha. = - degrees .beta. = 93.38(9) degrees .gamma. = - degrees Space group P2 1 Molecules/asymmetric unit 1 wherein measurement of said crystalline structure is at -50°C and which is characterized by fractional atomic coordinates substantially as listed in Table 8. 6. The crystalline structure EG (SB-2) having the formula le: characterized by one or more unit cell parameters substantially equal to the following: Cell dimensions: a = 11.4950(1) .ANG. b = 4.7443(1).ANG. c = 44.4154(5) .ANG. .alpha. = - degrees .beta.= - degrees .gamma.= - degrees Space group P2 1 2 1 2 1 Molecules/asymmetric unit 1 wherein measurement of said crystalline structure is at room temperature and which is characterized by fractional atomic coordinates substantially as listed in Table 10. 7. The crystalline structure 1:2 L-proline complex having the formula Ih (form 3): -104- characterized by one or more of the following: Cell dimensions (at -60°C): a= 10.311(1).ANG. b = 11.334(1) .ANG. c = 27.497(1) .ANG. .alpha. = 95.94 degrees .beta.= 99.22 degrees .gamma. = 90 degrees Space group = P1 Molecules/asymmetric unit 4 which is characterized by fractional atomic coordinates as listed in Table 15A; a) a powder x-ray diffraction pattern comprising 2.theta. values (CuK.alpha..lambda. = 1.5418 .ANG.) selected from the group consisting of 3.3 ~ 0.1, 6.5 ~ 0.1, 8.6 ~ 0.1, 15.7 ~ 0.1, 16.4 ~ 0.1, 17.2 ~ 0.1, 18.9 ~ 0.1, 19.8 ~ 0.1 and 20.3 ~ 0.1, at room temperature; b) a differential scanning calorimetry thermogram having an endotherm of 185°C or as shown in Figure 19; or c) thermal gravimetric analysis curve with negligible weight loss up to 150°C or as shown in Figure 16; 8. The crystalline structure 1:1 L-proline complex having structural formula Ii (form 6): -105- characterized by one or more of the following: Cell dimensions (at -40°C): a = 11