Methanesulfonyl chloride → 4-(2-tert-Butoxycarbonylamino-2-cyclohexyl-acetyl)-1-methanesulfonyl-octahydro-pyrrolo[3,2-b]pyrrole-3-carboxylic acid methyl ester

HRID 446968Notes

Reaction equation

HRID 446968 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:9][NH:8][CH:7]2[CH2:10][CH2:11][N:12]([C:13](=[O:29])[CH:14]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]3)[CH:6]12)=[O:4].CCN(C(C)C)C(C)C.[CH3:39][S:40](Cl)(=[O:42])=[O:41]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:1][O:2][C:3]([CH:5]1[CH2:9][N:8]([S:40]([CH3:39])(=[O:42])=[O:41])[CH:7]2[CH2:10][CH2:11][N:12]([C:13](=[O:29])[CH:14]([NH:21][C:22]([O:24][C:25]([CH3:26])([CH3:28])[CH3:27])=[O:23])[CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]3)[CH:6]12)=[O:4]

Participants

6

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 672807484-(2-tert-Butoxycarbonylamino-2-cyclohexyl-acetyl)-octahydro-pyrrolo[3,2-b]pyrrole-3-carboxylic acid methyl ester

Product 1

HCID 672807304-(2-tert-Butoxycarbonylamino-2-cyclohexyl-acetyl)-1-methanesulfonyl-octahydro-pyrrolo[3,2-b]pyrrole-3-carboxylic acid methyl esterYield 102.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 27 (0.9 g, 2.2 mmol) in DCM (20 mL) was cooled to 0° C. and treated with DIPEA (0.75 mL, 4.3 mmol) and DMAP (31 mg, 0.25 mmol). Methanesulfonyl chloride (0.3 mL, 3.9 mmol) was then added. After 1.5 h, the solution was diluted with DCM, washed successively with 1M HCl, brine, dried over anhydrous Na2SO4, filtered and concentrated to afford sulfonamide 28 as an off-white foam (1.1 g) which was used without further purification. 1H NMR (CDCl3, 300 MHz): δ5.23 (d, J=9.0 Hz, 1H), 4.74 (d, J=5.1 Hz, 1H), 4.31-4.28 (m, 2H), 4.03 (app t, J=9.3 Hz, 1H), 3.83-3.76 (m, 1H), 3.76 (s, 3H), 3.59-3.47 (m, 2H), 3.42-3.4 (m, 1H), 2.91 (s, 3H), 2.51 (dd, J=5.7, 13.8 Hz, 1H), 2.09-2.05 (m, 1H), 1.75-1.53 (m, 6H), 1.43 (s, 9H), 1.26-1.04 (m, 6H) ppm; 13C NMR (CDCl3, 75 MHz): δ172.7, 171.6, 155.9, 79.8, 66.1, 63.1, 56.9, 52.8, 50.7, 47.2, 46.2, 41.2, 35.6, 33.3, 29.8, 28.5, 28.4, 26.2, 26.1, 26.0 ppm.

Workup

  1. washwashed successively with 1M HCl, brine
  2. dry with materialdried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-3dfb6394534c446fa21e28dba00184b5
Source dataset
uspto-grants-2013_07
Patent number
US08481495B2

Reaction notes

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