Diisopropylethylamine → HCID 72338317, compound

HRID 2039266Notes

Reaction equation

HRID 2039266 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]

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 72338317HCID 72338317, compoundYield 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 C40H44F6N8O6: 846.82; observed [M+1]+: 847.34.

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-f29f6787fe0c47cbac050d507d6a6b46
Source dataset
uspto-grants-2013_11
Patent number
US08575118B2

Reaction notes

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