Ethanol → Isopropylaminium

HRID 537553Notes

Reaction equation

HRID 537553 reaction equation
[CH:1]1([CH:7]([NH:22][C:23]2[CH:24]=[N:25][C:26]([N:29]3[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[N:30]3)=[CH:27][CH:28]=2)[C:8]2[CH:21]=[CH:20][C:11]([C:12]([NH:14][CH2:15][CH2:16][C:17]([OH:19])=[O:18])=[O:13])=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(O)C.[CH:41]([NH2:44])([CH3:43])[CH3:42]>C(=O)=O>[CH:1]1([CH:7]([NH:22][C:23]2[CH:24]=[N:25][C:26]([N:29]3[CH:33]=[C:32]([C:34]([F:35])([F:36])[F:37])[CH:31]=[N:30]3)=[CH:27][CH:28]=2)[C:8]2[CH:9]=[CH:10][C:11]([C:12]([NH:14][CH2:15][CH2:16][C:17]([OH:19])=[O:18])=[O:13])=[CH:20][CH:21]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:41]([NH3+:44])([CH3:43])[CH3:42]

Participants

6

Reactant 3

HCID 702EthanolHCID 6363IsopropylamineHCID 60152084HCID 60152084, compound

Product 2

HCID 3364502IsopropylaminiumHCID 60152084HCID 60152084, compound

Reagents, catalysts & solvents 1

HCID 280Carbon DioxideSolvent

Procedure

(+\)-3-(4-(cyclohexyl(6-(4-(trifluoromethyl)-1H-pyrazol-1-yl)pyridine-3-ylamino)methyl)benzamido)propanoic acid (Example 101) was resolved by SFC (Column: Chiralpak AD-H 25×4.6 mm; mobile phase: 25% ethanol in CO2; modifier: 0.2% isopropylamine; flow rate: 2.5 mL/min) to provide 3-(4-(cyclohexyl(6-(4-(trifluoromethyl)-1H-pyrazol-1-yl)pyridine-3-ylamino)methyl)benzamido)propanoic acid, Isomer 1 (retention time: 6.93 min) and 3-(4-(cyclohexyl(6-(4-(trifluoromethyl)-1H-pyrazol-1-yl)pyridine-3-ylamino)methyl)benzamido)propanoic acid, Isomer 2 (retention time: 9.58 min) as their isopropylammonium salts. The salts were dissolved in water and the pH adjusted to 3.5 by addition of 1N aqueous HCl. The mixtures were extracted with dichloromethane. The organic layers were dried over MgSO4 and concentrated to provide 3-(4-(cyclohexyl(6-(4-(trifluoromethyl)-1H-pyrazol-1-yl)pyridine-3-ylamino)methyl)benzamido)propanoic acid, Isomer 1 and 3-(4-(cyclohexyl(6-(4-(trifluoromethyl)-1H-pyrazol-1-yl)pyridine-3-ylamino)methyl)benzamido)propanoic acid, Isomer 2. Spectral data for Isomer 1: 1H NMR (400 MHz, CDCl3) δ 8.58 (s, 1H), 7.77 (s, 1H), 7.65-7.72 (m, 3H), 7.60 (d, J=8.8 Hz), 7.32 (d, J=8.2 Hz, 2H), 6.82-6.88 (m, 1H), 6.71-6.78 (m, 1H), 4.15 (d, J=6.2 Hz, 1H), 3.65-3.73 (m, 2H), 2.63-2.73 (m, 2H), 1.83-1.93 (m, 1H), 1.59-1.82 (m, 4H), 1.46-1.56 (m, 1H), 0.94-1.28 (m, 6H). MS (M+H)=516.2.

Sources & evidence

ORD record
ord-e4cec7ae28d84436a47ca59ed6ab53e0
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Reaction notes

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