Butyl chloroformate → Buloxibutid

HRID 1993833Notes

Reaction equation

HRID 1993833 reaction equation
[N:1]1([CH2:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:17]=[C:16]([CH2:18][CH:19]([CH3:21])[CH3:20])[S:15][C:14]=3[S:22]([NH2:25])(=[O:24])=[O:23])=[CH:9][CH:8]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.N1(C2C=CC=CN=2)CCCC1.Cl[C:38]([O:40][CH2:41][CH2:42][CH2:43][CH3:44])=[O:39]>N1C=CC=CC=1>[CH2:41]([O:40][C:38]([NH:25][S:22]([C:14]1[S:15][C:16]([CH2:18][CH:19]([CH3:21])[CH3:20])=[CH:17][C:13]=1[C:10]1[CH:11]=[CH:12][C:7]([CH2:6][N:1]2[CH:5]=[CH:4][N:3]=[CH:2]2)=[CH:8][CH:9]=1)(=[O:24])=[O:23])=[O:39])[CH2:42][CH2:43][CH3:44]

Participants

5

Reactant 3

HCID 61140Butyl chloroformateHCID 110190202-(Pyrrolidin-1-yl)pyridineHCID 113947443(4-Imidazol-1-ylmethylphenyl)5-iso-butylthiophene-2 sulfonamide

Product 1

HCID 9804984BuloxibutidYield 46.5%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

The crude 3-(4-imidazol-1-ylmethylphenyl)-5-iso-butylthiophene-2-sulfonamide from step (f) above was dissolved in pyridine (2 mL, dried over 4 Å molecular sieve). Pyrrolidinopyridine (40.52 mg, 0.2618 mmol) and butyl chloroformate (363.5 mg, 0.339 mL) were added to the mixture. The mixture was stirred overnight under a N2 atmosphere at room temperature. Evaporation and co-evaporation with acetonitrile to remove the solvents and purification on column chromatography with 10% MeOH in chloroform as eluent gave the title compound (57.8 mg, 0.1217 mmol) in a 46.5% yield (over the last two steps).

Workup

  1. customEvaporation and co-evaporation with acetonitrile
  2. customto remove
  3. customthe solvents and purification on column chromatography with 10% MeOH in chloroform as eluent

Sources & evidence

ORD record
ord-e34173c64ee34f7ea979ba02f3f4ebe6
Source dataset
uspto-grants-2010_01
Patent number
US07652054B2

Reaction notes

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