4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic Acid → N-[2-amino-1-(phenylmethyl)ethyl]-N-methyl-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide

HRID 2392007Notes

Reaction equation

HRID 2392007 reaction equation
Cl.[NH2:2][C@@H:3]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1C(F)(F)F)[CH2:4][N:5]1C(=O)C2C(=CC=CC=2)C1=O.[CH3:27][N:28]1[C:32]([C:33]2[CH:34]=[C:35]([C:38]([OH:40])=O)[S:36][CH:37]=2)=[CH:31][CH:30]=[N:29]1.Br[C:42]1C=C(C(O)=O)SC=1C1N(C)N=CC=1>>[NH2:5][CH2:4][CH:3]([N:2]([CH3:42])[C:38]([C:35]1[S:36][CH:37]=[C:33]([C:32]2[N:28]([CH3:27])[N:29]=[CH:30][CH:31]=2)[CH:34]=1)=[O:40])[CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

4

Reactant 3

HCID 578264554-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic AcidHCID 578265674-bromo-5-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic AcidHCID 670654562-{(2s)-2-Amino-3-[2-(trifluoromethyl)phenyl]propyl}-1h-isoindole-1,3(2h)-dione-hcl

Product 1

HCID 24995006N-[2-amino-1-(phenylmethyl)ethyl]-N-methyl-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide

Procedure

The title compound was prepared as a white solid according to the procedure of Example 6, except substituting 2-[2-(methylamino)-3-phenylpropyl]-1H-isoindole-1,3(2H)-dione (200 mg, 0.7 mmol)[prepared according to the procedure of Preparation 6] for 2-{(2S)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione-HCl and substituting 4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic acid (150 mg, 0.72 mmol) for 4-bromo-5-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic acid. The reaction mixture was absorbed onto silica and purified via column chromatography (silica, 3% MeOH in DCM (1% NH4OH)) yielding the title compound, which was further purified by Gilson reverse phase chromatography 5-95% H2O (1% TFA)/MeCN (1% TFA) to afford the TFA salt: LC-MS (ES) m/z 355 (M+H)+, 1H NMR (400 MHz, MeOD) δ ppm 2.86 (s, 3H) 2.97 (dd, J=14.02, 8.72 Hz, 2H) 3.12-3.23 (m, 2H) 3.70 (m, 1H) 3.97 (s, 3H) 6.47 (d, J=2.02 Hz, 1H) 7.30-7.35 (m, 1H) 7.37-7.43 (m, 5H) 7.51 (d, J=2.02 Hz, 1H) 7.88 (d, J=1.52 Hz, 1H) 7.94 (d, J=1.52 Hz, 1H).

Workup

  1. customThe title compound was prepared as a white solid
  2. customprepared
  3. customThe reaction mixture was absorbed onto silica
  4. custompurified via column chromatography (silica, 3% MeOH in DCM (1% NH4OH))

Sources & evidence

ORD record
ord-aeb41fe115964df18e39dc9c9ba6a8ac
Source dataset
uspto-grants-2012_09
Patent number
US08273782B2

Reaction notes

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