Diisopropylethylamine → methyl 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 1855642Notes

Reaction equation

HRID 1855642 reaction equation
[CH3:1][C:2]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=3)=[CH:18][CH:17]=2)[CH2:10][CH2:9]1)([CH3:7])[C:3]([O:5][CH3:6])=[O:4].[F:33][C:34]1[C:39]([F:40])=[CH:38][CH:37]=[CH:36][C:35]=1[CH2:41][CH2:42][C:43]1[N:48]([CH2:49][C:50](O)=[O:51])[C:47]2[N:53]=[CH:54][CH:55]=[CH:56][C:46]=2[C:45](=[O:57])[N:44]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[F:33][C:34]1[C:39]([F:40])=[CH:38][CH:37]=[CH:36][C:35]=1[CH2:41][CH2:42][C:43]1[N:48]([CH2:49][C:50]([N:14]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:23]=[CH:24][C:25]([O:28][C:29]([F:31])([F:32])[F:30])=[CH:26][CH:27]=3)=[CH:18][CH:17]=2)[CH:11]2[CH2:12][CH2:13][N:8]([C:2]([CH3:1])([CH3:7])[C:3]([O:5][CH3:6])=[O:4])[CH2:9][CH2:10]2)=[O:51])[C:47]2[N:53]=[CH:54][CH:55]=[CH:56][C:46]=2[C:45](=[O:57])[N:44]=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 59707041Methyl 2-methyl-2-{4-[({4'-[(trifluoromethyl)oxy]-4-biphenylyl}methyl)amino]-1-piperidinyl}propanoate

Product 1

HCID 24984026methyl 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 46.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of methyl 2-methyl-2-{4-[({4′-[(trifluoromethyl)oxy]-4-biphenylyl}methyl)amino]-l piperidinyl}propanoate (Int. B6) (145 mg, 1 equiv), [2-[2-(2,3-difluorophenyl)ethyl]-4-oxopyrido[2,3-d]pyrimidin-1(4H)-yl]acetic acid (Int. D1) (122 mg, 1 equiv), DIPEA (0.084 ml, 1.5 equiv) and DMF (2.0 ml) was stirred at room temperature for 5 min. The HATU (160 mg, 1.3 equiv) was added in 1 portion and stirred an additional 1 hour under nitrogen. The crude reaction mixture was applied directly to reverse-phase HPLC (Preparative Method A) to obtain methyl 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 (116 mg).

Workup

  1. stirringstirred an additional 1 hour under nitrogen
  2. customThe crude reaction mixture

Sources & evidence

ORD record
ord-6765d24251654e43b5df622d3f133d2d
Source dataset
uspto-grants-2015_02
Patent number
US08962633B2

Reaction notes

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