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Diisopropylethylamine → HCID 72338317, compound

HRID 2392476
Notes
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Reaction equation

HRID 2392476 reaction equation
[CH3:1][O:2][C:3](=[O:46])[NH:4][CH:5]([C:12]([N:14]1[CH2:18][CH2:17][CH2:16][CH:15]1[C:19]1[NH:20][C:21]([C:24]2[CH:29]=[CH:28][C:27]([C:30]3[CH:35]=[CH:34][C:33]([C:36]4[NH:37][C:38]([CH:41]5[CH2:45][CH2:44][CH2:43][NH:42]5)=[N:39][CH:40]=4)=[CH:32][CH:31]=3)=[CH:26][CH:25]=2)=[CH:22][N:23]=1)=[O:13])[CH2:6][CH2:7][C:8]([F:11])([F:10])[F:9].[F:47][C:48]([F:61])([F:60])[CH2:49][CH2:50][CH:51]([NH:55][C:56]([O:58][CH3:59])=[O:57])[C:52](O)=[O:53].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C)C=O>[CH3:59][O:58][C:56](=[O:57])[NH:55][CH:51]([C:52]([N:42]1[CH2:43][CH2:44][CH2:45][CH:41]1[C:38]1[NH:37][C:36]([C:33]2[CH:34]=[CH:35][C:30]([C:27]3[CH:26]=[CH:25][C:24]([C:21]4[NH:20][C:19]([CH:15]5[CH2:16][CH2:17][CH2:18][N:14]5[C:12](=[O:13])[CH:5]([NH:4][C:3]([O:2][CH3:1])=[O:46])[CH2:6][CH2:7][C:8]([F:9])([F:11])[F:10])=[N:23][CH:22]=4)=[CH:29][CH:28]=3)=[CH:31][CH:32]=2)=[CH:40][N:39]=1)=[O:53])[CH2:50][CH2:49][C:48]([F:47])([F:61])[F:60]
ParticipantsProcedureWorkupSources & evidenceReaction notes

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 66621118[4,4,4-Trifluoro-1-(2-{5-[4'-(2-pyrrolidin-2-yl-3H-imidazol-4-yl)-biphenyl-4-yl]-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl)-butyl]-carbamic acid methyl esterHCID 723382845,5,5-Trifluoro-2-methoxycarbonylamino-pentanoic acid

Product 1

HCID 72338317
HCID 72338317, compound
Yield 23%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of crude [4,4,4-Trifluoro-1-(2-{5-[4′-(2-pyrrolidin-2-yl-3H-imidazol-4-yl)-biphenyl-4-yl]-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl)-butyl]-carbamic acid methyl ester (115 mg, 0.18 mmol) in dimethylformamide (0.5 mL) was added a solution of 5,5,5-Trifluoro-2-methoxycarbonylamino-pentanoic acid (44 mg, 0.19 mmol) and HATU (72 mg, 0.19 mmol) in dimethylformamide (0.5 mL). Diisopropylethylamine (65 μL, 0.37 mmol) was then added and the reaction was stirred at room temperature for 16 hours. The solution was concentrated and purified by preparative reverse phase HPLC (Gemini, 15 to 50% ACN/H2O+0.1% HCO2H) to yield (4,4,4-Trifluoro-1-{2-[5-(4′-{2-[1-(5,5,5-trifluoro-2-methoxycarbonylamino-pentanoyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-butyl)-carbamic acid methyl ester (35 mg, 23%). LCMS-ESI+: calculated for CoH44F6N8O6: 846.82; observed [M+1]+ : 847.34. 1H-NMR: 400 MHz, (CD3OD) δ: 7.81-7.72 (m, 4H), 7.67-7.64 (m, 4H), 7.38-7.32 (m, 2H), 5.20-5.16 (m, 2H), 4.55-4.51 (m, 2H), 3.91-3.86 (m, 4H), 3.67 (s, 6H), 2.38-2.20 (m, 8H), 2.18-1.79 (m, 8H) ppm.

Workup

  1. concentrationThe solution was concentrated
  2. custompurified by preparative reverse phase HPLC (Gemini, 15 to 50% ACN/H2O+0.1% HCO2H)

Sources & evidence

ORD record
ord-2177a6a3e67d40c1bf27ff51b71e5d74
Source dataset
uspto-grants-2012_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08273341B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes