Diisopropylethylamine → 2-{5-[1-(Isoquinoline-5-sulfonyl)-piperidin-3-yl]-4'-trifluoromethyl-biphenyl-3-yl}-4-methyl-pentanoic acid ethyl ester

HRID 889717Notes

Reaction equation

HRID 889717 reaction equation
[CH2:1]([O:3][C:4](=[O:32])[CH:5]([C:10]1[CH:11]=[C:12]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=2)[CH:13]=[C:14]([CH:16]2[CH2:21][CH2:20][CH2:19][NH:18][CH2:17]2)[CH:15]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])[CH3:2].[CH:33]1[C:42]2[CH:41]=[CH:40][CH:39]=[C:38]([S:43](Cl)(=[O:45])=[O:44])[C:37]=2[CH:36]=[CH:35][N:34]=1.CCN(C(C)C)C(C)C>ClCCl>[CH2:1]([O:3][C:4](=[O:32])[CH:5]([C:10]1[CH:11]=[C:12]([C:22]2[CH:23]=[CH:24][C:25]([C:28]([F:29])([F:30])[F:31])=[CH:26][CH:27]=2)[CH:13]=[C:14]([CH:16]2[CH2:21][CH2:20][CH2:19][N:18]([S:43]([C:38]3[C:37]4[CH:36]=[CH:35][N:34]=[CH:33][C:42]=4[CH:41]=[CH:40][CH:39]=3)(=[O:44])=[O:45])[CH2:17]2)[CH:15]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])[CH3:2]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 33716555-Isoquinolinesulfonyl chlorideHCID 576660204-Methyl-2-(5-piperidin-3-yl-4'-trifluoromethyl-biphenyl-3-yl)-pentanoic acid ethyl ester

Product 1

HCID 576660492-{5-[1-(Isoquinoline-5-sulfonyl)-piperidin-3-yl]-4'-trifluoromethyl-biphenyl-3-yl}-4-methyl-pentanoic acid ethyl esterYield 88.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of compound 33b, 4-Methyl-2-(5-piperidin-3-yl-4′-trifluoromethyl-biphenyl-3-yl)-pentanoic acid ethyl ester (48.0 mg, 0.106mmol) in anhydrous dichloromethane (4 ml) was added isoquinoline -5-sulfonyl chloride (42.1 mg, 0.16 mmol) and DIEA (37.0 μl, 0.21 mmol). The reaction stirred at room temperature over 72 hours, was diluted with dichloromethane and washed with sat. NaHCO3, and brine, dried and filtered. Purification by silica gel chromatography (Isco) gave the desired product, (60.0 mg, 88% ). Calcd for C35H37F3N2O4S (M+H) 638.74, Found 639.3.

Workup

  1. washwashed with sat. NaHCO3, and brine
  2. customdried
  3. filtrationfiltered
  4. customPurification by silica gel chromatography (Isco)

Sources & evidence

ORD record
ord-974d4a8b3c754f4c93763636c602d9c1
Source dataset
uspto-grants-2012_08
Patent number
US08252935B2

Reaction notes

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