1,2-Dichloroethane → (1-{1-Cyclohexyl-2-[4-cyclopropanecarbonyl-6-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrol-1-yl]-2-oxo-ethylcarbamoyl}-ethyl) methyl-carbamic benzyl ester

HRID 446984Notes

Reaction equation

HRID 446984 reaction equation
[CH:1]1([NH:11][C:12]([CH:14]2[CH2:18][N:17]([C:19]([CH:21]3[CH2:23][CH2:22]3)=[O:20])[CH:16]3[CH2:24][CH2:25][N:26]([C:27](=[O:36])[CH:28]([NH2:35])[CH:29]4[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]4)[CH:15]23)=[O:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[C:37]([N:47]([CH3:53])[C@H:48]([C:50](O)=[O:51])[CH3:49])([O:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:38].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:40]([O:39][C:37](=[O:38])[N:47]([CH:48]([C:50](=[O:51])[NH:35][CH:28]([CH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1)[C:27]([N:26]1[CH2:25][CH2:24][CH:16]2[N:17]([C:19]([CH:21]3[CH2:22][CH2:23]3)=[O:20])[CH2:18][CH:14]([C:12](=[O:13])[NH:11][CH:1]3[C:10]4[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=4)[CH2:4][CH2:3][CH2:2]3)[CH:15]12)=[O:36])[CH3:49])[CH3:53])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7016365Z-N-Me-Ala-OHHCID 672813634-(2-Amino-2-cyclohexyl-acetyl)-1-cyclopropanecarbonyl-octahydro-pyrrolo[3,2-b]pyrrole-3-carboxylic acid (1,2,3,4-tetrahydro-naphthalen-1-yl)-amide

Product 1

HCID 67282642(1-{1-Cyclohexyl-2-[4-cyclopropanecarbonyl-6-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrol-1-yl]-2-oxo-ethylcarbamoyl}-ethyl) methyl-carbamic benzyl esterYield 95.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 47 (330 mg, 0.67 mmol) in DCM (10 mL) was cooled to 0° C. and treated with Cbz-N(Me)Ala-OH (159 mg, 0.67 mmol), EDC (154 mg, 0.80 mmol), HOBt (109 mg, 0.80 mmol) and DIPEA (0.36 mL, 2.08 mmol), respectively. After 18 h, the solution was diluted with DCM, washed successively with 1M HCl, saturated aqueous NaHCO3, and brine, dried over anhydrous Na2SO4, filtered and concentrated to afford 48 (454 mg) as a white foam that was used without further purification. Mass spectrum, m/z [712.9] (M+H)+.

Workup

  1. washwashed successively with 1M HCl, saturated aqueous NaHCO3, and brine
  2. dry with materialdried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-54d1943492004668a2bff5e9cedb9c4c
Source dataset
uspto-grants-2013_07
Patent number
US08481495B2

Reaction notes

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