Methanesulfonyl chloride → (1-{1-[6-(3,4-Difluoro-phenoxy)-4-methanesulfonyl-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propylcarbamoyl}-ethyl)-methyl-carbamic acid benzyl ester

HRID 1965181Notes

Reaction equation

HRID 1965181 reaction equation
[CH2:1]([O:8][C:9](=[O:41])[N:10]([CH:12]([C:14](=[O:40])[NH:15][CH:16]([C:21]([N:23]1[CH2:27][CH2:26][CH:25]2[NH:28][CH2:29][CH:30]([O:31][C:32]3[CH:37]=[CH:36][C:35]([F:38])=[C:34]([F:39])[CH:33]=3)[CH:24]12)=[O:22])[C:17]([CH3:20])([CH3:19])[CH3:18])[CH3:13])[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[CH3:51][S:52](Cl)(=[O:54])=[O:53]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH2:1]([O:8][C:9](=[O:41])[N:10]([CH:12]([C:14](=[O:40])[NH:15][CH:16]([C:21]([N:23]1[CH2:27][CH2:26][CH:25]2[N:28]([S:52]([CH3:51])(=[O:54])=[O:53])[CH2:29][CH:30]([O:31][C:32]3[CH:37]=[CH:36][C:35]([F:38])=[C:34]([F:39])[CH:33]=3)[CH:24]12)=[O:22])[C:17]([CH3:19])([CH3:18])[CH3:20])[CH3:13])[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 67606709(1-{1-[6-(3,4-Difluoro-phenoxy)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propylcarbamoyl}-ethyl)-methyl-carbamic acid benzyl ester

Product 1

HCID 67608849(1-{1-[6-(3,4-Difluoro-phenoxy)-4-methanesulfonyl-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propylcarbamoyl}-ethyl)-methyl-carbamic acid benzyl esterYield 73%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution containing 35 (228 mg, 0.4 mmol), DIPEA (104 mg, 0.8 mmol) and DMAP (cat) in DCM (5 mL) was cooled to 0° C. Methanesulfonyl chloride (55 mg, 0.48 mmol) was added. After 1 h, the reaction mixture was warmed to ambient temperature, diluted with DCM, washed successively with saturated aqueous NaHCO3, 1N HCl, and brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by RP-HPLC (2″ Dynamax® C18; 10-100% ACN/water containing 0.1% HOAc over 30 min; Flow: 40 mL/min) to afford compound 36 (190 mg) as a white solid. Mass spectrum, m/z [651.1] (M+H)+.

Workup

  1. temperaturethe reaction mixture was warmed to ambient temperature
  2. washwashed successively with saturated aqueous NaHCO3, 1N HCl, and brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by RP-HPLC (2″ Dynamax® C18
  7. wait10-100% ACN/water containing 0.1% HOAc over 30 min

Sources & evidence

ORD record
ord-21b4e1b32baa4f0c93946a4fecf95817
Source dataset
uspto-grants-2013_04
Patent number
US08415486B2

Reaction notes

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