Diisopropylethylamine → 1-methylethyl 2-[4-({[2-[2-(2,3-difluorophenyl)ethyl]-4-oxopyrido[2,3-d]pyrimidin-1(4H)-yl]acetyl}{[4'-(trifluoromethyl)-4-biphenylyl]methyl}amino)-1-piperidinyl]-2-methylpropanoate

HRID 1855640Notes

Reaction equation

HRID 1855640 reaction equation
[CH3:1][C:2]([N:10]1[CH2:15][CH2:14][CH:13]([NH:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=3)=[CH:20][CH:19]=2)[CH2:12][CH2:11]1)([CH3:9])[C:3]([O:5][CH:6]([CH3:8])[CH3:7])=[O:4].[F:34][C:35]1[C:40]([F:41])=[CH:39][CH:38]=[CH:37][C:36]=1[CH2:42][CH2:43][C:44]1[N:49]([CH2:50][C:51](O)=[O:52])[C:48]2[N:54]=[CH:55][CH:56]=[CH:57][C:47]=2[C:46](=[O:58])[N:45]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[F:34][C:35]1[C:40]([F:41])=[CH:39][CH:38]=[CH:37][C:36]=1[CH2:42][CH2:43][C:44]1[N:49]([CH2:50][C:51]([N:16]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][C:27]([C:30]([F:32])([F:31])[F:33])=[CH:26][CH:25]=3)=[CH:20][CH:19]=2)[CH:13]2[CH2:14][CH2:15][N:10]([C:2]([CH3:1])([CH3:9])[C:3]([O:5][CH:6]([CH3:8])[CH3:7])=[O:4])[CH2:11][CH2:12]2)=[O:52])[C:48]2[N:54]=[CH:55][CH:56]=[CH:57][C:47]=2[C:46](=[O:58])[N:45]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11187030[2-[2-(2,3-difluorophenyl)ethyl]-4-oxopyrido[2,3-d]pyrimidin-1(4H)-yl]acetic acidHCID 597070421-Methylethyl 2-methyl-2-[4-({[4'-(trifluoromethyl)-4-biphenylyl]methyl}amino)-1-piperidinyl]propanoate

Product 1

HCID 248123541-methylethyl 2-[4-({[2-[2-(2,3-difluorophenyl)ethyl]-4-oxopyrido[2,3-d]pyrimidin-1(4H)-yl]acetyl}{[4'-(trifluoromethyl)-4-biphenylyl]methyl}amino)-1-piperidinyl]-2-methylpropanoateYield 24.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 1-methylethyl 2-methyl-2-[4-({[4′-(trifluoromethyl)-4-biphenylyl]methyl}-amino)-1-piperidinyl]propanoate (Int. B3) (420 mg, 1 equiv), [2-[2-(2,3-difluorophenyl)-ethyl]-4-oxopyrido[2,3-d]pyrimidin-1(4H)-yl]acetic acid (Int. D1) (300 mg, 1 equiv), HATU (396 mg, 1.2 equiv), DIPEA (0.22 ml, 1.5 equiv) and DMF (3.0 ml) was stirred at room temperature for 30 min. The crude reaction mixture was applied directly to reverse-phase HPLC (Preparative Method A) to obtain 1-methylethyl 2-[4-({[2-[2-(2,3-difluorophenyl)ethyl]-4-oxopyrido[2,3-d]pyrimidin-1(4H)-yl]acetyl}{[4′-(trifluoromethyl)-4-biphenylyl]methyl}amino)-1-piperidinyl]-2-methylpropanoate (171 mg).

Workup

  1. customThe crude reaction mixture

Sources & evidence

ORD record
ord-4ae5756c937c45fda672ec748f290fdd
Source dataset
uspto-grants-2015_02
Patent number
US08962633B2

Reaction notes

Loading…