Sodium hydride → 1-Methyl-1H-pyrazole-4-sulfonic acid 4-[2-(4-bromo-benzyl)-4,5-dimethyl-thiophene-3-carbonyl]-2-cyclopentyl-phenyl Ester

HRID 1067375Notes

Reaction equation

HRID 1067375 reaction equation
[Br:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][C:7]2[S:8][C:9]([CH3:27])=[C:10]([CH3:26])[C:11]=2[C:12]([C:14]2[CH:19]=[CH:18][C:17]([OH:20])=[C:16]([CH:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)[CH:15]=2)=[O:13])=[CH:4][CH:3]=1.[H-].[Na+].[CH3:32][N:33]1[CH:37]=[C:36]([S:38](Cl)(=[O:40])=[O:39])[CH:35]=[N:34]1>>[Br:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][C:7]2[S:8][C:9]([CH3:27])=[C:10]([CH3:26])[C:11]=2[C:12]([C:14]2[CH:19]=[CH:18][C:17]([O:20][S:38]([C:36]3[CH:35]=[N:34][N:33]([CH3:32])[CH:37]=3)(=[O:40])=[O:39])=[C:16]([CH:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)[CH:15]=2)=[O:13])=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 24758Sodium hydrideHCID 15895037[2-(4-Bromobenzyl)-4,5-dimethyl-thiophen-3-yl]-(3-cyclopentyl4-hydroxy-phenyl)-methanoneHCID 170247301-methyl-1H-pyrazole-4-sulfonyl chloride

Product 1

HCID 98951831-Methyl-1H-pyrazole-4-sulfonic acid 4-[2-(4-bromo-benzyl)-4,5-dimethyl-thiophene-3-carbonyl]-2-cyclopentyl-phenyl EsterYield 55%

Procedure

At ambient temperature, to a stirred solution of [2-(4-bromobenzyl)-4,5-dimethyl-thiophen-3-yl]-(3-cyclopentyl-4-hydroxy-phenyl)-methanone (0.283 g, 0.603 mmol) in N,N-DMF (3.0 mL) was added 60% sodium hydride/mineral oil (24.1 mg, 0.603 mmol). After 0.5 h, to the reaction was added a solution of 1-methyl-1H-pyrazole-4-sulfonyl chloride (0.120 g, 0.664 mmol) in N,N-DMF (1.3 mL). After 3 h, the reaction was quenched with 1N NaOH (40 mL), extracted with CH2Cl2, dried (Na2SO4) and concentrated. Purification on Biotage KP-Sil eluting with 20% acetone/hexane gave 0.202 g (55%) of the title compound as a yellow solid, mp 55-60° C. (DMSO-d6) δ1.29-1.34 (m, 2H), 1.59-1.79 (m, 6H), 1.81 (s, 3H), 2.28 (s, 3H), 3.08 (quintet, 1H), 3.87 (s, 2H), 3.89 (s, 3H), 6.98 (d, 2H), 7.32 (d, 1H), 7.39 (d, 2H), 7.53-7.57 (m, 2H), 7.97 (s, 1H), 8.62 (s, 1H). IR (KBr) 3450, 2950, 1650, 1490, 1400, 1370 and 1170 cm−1. mass spectrum (+ESI) m/z 613/615 (M+H).

Workup

  1. waitAfter 3 h
  2. customthe reaction was quenched with 1N NaOH (40 mL)
  3. extractionextracted with CH2Cl2
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customPurification on Biotage KP-Sil
  7. washeluting with 20% acetone/hexane

Sources & evidence

ORD record
ord-d499967af8a5486899fe7ddfa9bffece
Source dataset
uspto-grants-2001_06
Patent number
US06248764B1

Reaction notes

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