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

HRID 573492Notes

Reaction equation

HRID 573492 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]([O:30][C:31]([F:34])([F:33])[F:32])=[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:35][C:36]1[C:41]([F:42])=[CH:40][CH:39]=[CH:38][C:37]=1[CH2:43][CH2:44][C:45]1[N:50]([CH2:51][C:52](O)=[O:53])[C:49]2[N:55]=[CH:56][CH:57]=[CH:58][C:48]=2[C:47](=[O:59])[N:46]=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:35][C:36]1[C:41]([F:42])=[CH:40][CH:39]=[CH:38][C:37]=1[CH2:43][CH2:44][C:45]1[N:50]([CH2:51][C:52]([N:16]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:25]=[CH:26][C:27]([O:30][C:31]([F:33])([F:32])[F:34])=[CH:28][CH:29]=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:53])[C:49]2[N:55]=[CH:56][CH:57]=[CH:58][C:48]=2[C:47](=[O:59])[N:46]=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 597070381-Methylethyl 2-methyl-2-{4-[({4'-[(trifluoromethyl)oxy]-4-biphenylyl}methyl)amino]-1-piperidinyl}propanoate

Product 1

HCID 248124451-methylethyl 2-{4-[{[2-[2-(2,3-difluorophenyl)ethyl]-4-oxopyrido[2,3-d]pyrimidin-1(4H)-yl]acetyl}({4'-[(trifluoromethyl)oxy]-4-biphenylyl} methyl)amino]-1-piperidinyl}-2-methylpropanoateYield 18.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 1-methylethyl 2-methyl-2-{4-[({4′-[(trifluoromethyl)oxy]-4-biphenylyl}methyl)-amino]-1-piperidinyl}propanoate (Int. B5) (80 mg, 1 equiv), [2-[2-(2,3-difluorophenyl)ethyl]-4-oxopyrido[2,3-d]pyrimidin-1(4H)-yl]acetic acid (Int. D1) (67 mg, 1 equiv), HATU (400 mg, 5 equiv), DIPEA (0.22 ml, 1.5 equiv) and DMF (2.0 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)oxy]-4-biphenylyl}methyl)amino]-1-piperidinyl}-2-methylpropanoate (25 mg).

Workup

  1. customThe crude reaction mixture

Sources & evidence

ORD record
ord-3d0d63eabafd4c9b827b0c9e526de203
Source dataset
uspto-grants-2015_05
Patent number
US09029383B2

Reaction notes

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