Methyl 3-aminopropanoate hydrochloride → methyl 3-(6-(cyclohexyl(2-methyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methylamino)nicotinamido)propanoate

HRID 537547Notes

Reaction equation

HRID 537547 reaction equation
[CH:1]1([N:7]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([N:25]3[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[N:26]3)=[CH:21][C:20]=2[CH3:34])[C:8]2[CH:17]=[CH:16][C:11]([C:12](OC)=[O:13])=[CH:10][N:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[NH2:36][CH2:37][CH2:38][C:39]([O:41][CH3:42])=[O:40]>>[CH:1]1([N:7]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([N:25]3[CH:29]=[C:28]([C:30]([F:31])([F:33])[F:32])[CH:27]=[N:26]3)=[CH:21][C:20]=2[CH3:34])[C:8]2[CH:17]=[CH:16][C:11]([C:12]([NH:36][CH2:37][CH2:38][C:39]([O:41][CH3:42])=[O:40])=[O:13])=[CH:10][N:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

3

Reactant 2

HCID 2734767Methyl 3-aminopropanoate hydrochlorideHCID 86669088(+/-)-methyl 6-(cyclohexyl(2-methyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methylamino)nicotinate

Product 1

HCID 68157932methyl 3-(6-(cyclohexyl(2-methyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methylamino)nicotinamido)propanoate

Procedure

The title compound was prepared by a method analogous to that described in Steps B-C of Example 82, using (+/−)-methyl 6-(cyclohexyl(2-methyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methylamino)nicotinate in Step B and methyl 3-aminopropanoate hydrochloride in Step C. Racemic methyl 3-(6-(cyclohexyl(2-methyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methylamino)nicotinamido)propanoate was purified by chiral SFC to afford Isomer 1 and Isomer 2, which were used in conversion to the final enantiopure products. Chiral SFC: Chiralpak AD-H, 4.6×250 mm, 5 μm. Modifier 0.05% DEA. Mobile Phase: 60/40 CO/ethanol. Flow: 2.35 mL/min. Retention time: 5.19 minutes (Isomer 1) and 7.83 minutes (Isomer 2).

Workup

  1. customRacemic methyl 3-(6-(cyclohexyl(2-methyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methylamino)nicotinamido)propanoate was purified by chiral SFC
  2. customto afford Isomer 1 and Isomer 2, which
  3. customRetention time: 5.19 minutes (Isomer 1) and 7.83 minutes (Isomer 2)

Sources & evidence

ORD record
ord-7cc7350696fa48bc937f10c29128ed64
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Reaction notes

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