Diisopropylethylamine → methyl 2-[4-({[2-[2-(2,3-difluorophenyl)ethyl]-4-oxo-1(4H)-quinazolinyl]acetyl}{[4'-(trifluoromethyl)-4-biphenylyl]methyl}amino)-1-piperidinyl]-2-methylpropanoate

HRID 646205Notes

Reaction equation

HRID 646205 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][C:11]1[N:12]([CH2:22][C:23]([OH:25])=O)[C:13]2[C:18]([C:19](=[O:21])[N:20]=1)=[CH:17][CH:16]=[CH:15][CH:14]=2.[CH3:26][C:27]([N:33]1[CH2:38][CH2:37][CH:36]([NH:39][CH2:40][C:41]2[CH:46]=[CH:45][C:44]([C:47]3[CH:52]=[CH:51][C:50]([C:53]([F:56])([F:55])[F:54])=[CH:49][CH:48]=3)=[CH:43][CH:42]=2)[CH2:35][CH2:34]1)([CH3:32])[C:28]([O:30][CH3:31])=[O:29].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>C(#N)C>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][C:11]1[N:12]([CH2:22][C:23]([N:39]([CH2:40][C:41]2[CH:46]=[CH:45][C:44]([C:47]3[CH:48]=[CH:49][C:50]([C:53]([F:56])([F:54])[F:55])=[CH:51][CH:52]=3)=[CH:43][CH:42]=2)[CH:36]2[CH2:37][CH2:38][N:33]([C:27]([CH3:26])([CH3:32])[C:28]([O:30][CH3:31])=[O:29])[CH2:34][CH2:35]2)=[O:25])[C:13]2[C:18]([C:19](=[O:21])[N:20]=1)=[CH:17][CH:16]=[CH:15][CH:14]=2

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 58788314HCID 58788314, compoundHCID 59264602HCID 59264602, compound

Product 1

HCID 24771861methyl 2-[4-({[2-[2-(2,3-difluorophenyl)ethyl]-4-oxo-1(4H)-quinazolinyl]acetyl}{[4'-(trifluoromethyl)-4-biphenylyl]methyl}amino)-1-piperidinyl]-2-methylpropanoateYield 57.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of [2-[2-(2,3-difluorophenyl)ethyl]-4-oxo-1 (4H)-quinazolinyl]acetic acid (Int. C1) (100 mg, 1 equiv), methyl 2-methyl-2-[4-({[4′-(trifluoromethyl)-4-biphenylyl]methyl}amino)-1-piperidinyl]propanoate (Int. B1) (130 mg, 1.03 equiv), DIPEA (0.1 ml, 3.6 equiv), acetonitrile (2 ml) and HATU (130 mg, 1.4 equiv) was stirred at room temperature for 1 h, then evaporated and redissolved in acetonitrile. Purification by reverse phase HPLC (Preparative Method A) gave methyl 2-[4-({[2-[2-(2,3-difluoro-phenyl)ethyl]-4-oxo-1 (4H)-quinazolinyl]acetyl} {[4′-(trifluoromethyl)-4-biphenylyl]-methyl}amino)-1-piperidinyl]-2-methylpropanoate (128 mg).

Workup

  1. customevaporated
  2. dissolutionredissolved in acetonitrile
  3. customPurification by reverse phase HPLC (Preparative Method A)

Sources & evidence

ORD record
ord-4ae0576100984892b700de84a1346716
Source dataset
uspto-grants-2010_04
Patent number
US07705005B2

Reaction notes

Loading…