1,2-Dichloroethane → 1-(2-{2-[(3-acetyl-4,5-dimethyl-1H-pyrrole-2-carbonyl)-amino]-2-cyclohexyl-acetylamino}-3,3-dimethyl-butyryl)-octahydro-indole-2-carboxylic acid tert-butyl ester

HRID 917800Notes

Reaction equation

HRID 917800 reaction equation
[C:1]([C:4]1[C:8]([CH3:9])=[C:7]([CH3:10])[NH:6][C:5]=1[C:11]([OH:13])=O)(=[O:3])[CH3:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[C:28]([O:32][C:33]([CH:35]1[CH2:43][CH:42]2[CH:37]([CH2:38][CH2:39][CH2:40][CH2:41]2)[N:36]1[C:44](=[O:61])[CH:45]([NH:50][C:51](=[O:60])[CH:52]([NH2:59])[CH:53]1[CH2:58][CH2:57][CH2:56][CH2:55][CH2:54]1)[C:46]([CH3:49])([CH3:48])[CH3:47])=[O:34])([CH3:31])([CH3:30])[CH3:29]>CN(C=O)C>[C:28]([O:32][C:33]([CH:35]1[CH2:43][CH:42]2[CH:37]([CH2:38][CH2:39][CH2:40][CH2:41]2)[N:36]1[C:44](=[O:61])[CH:45]([NH:50][C:51](=[O:60])[CH:52]([NH:59][C:11]([C:5]1[NH:6][C:7]([CH3:10])=[C:8]([CH3:9])[C:4]=1[C:1](=[O:3])[CH3:2])=[O:13])[CH:53]1[CH2:54][CH2:55][CH2:56][CH2:57][CH2:58]1)[C:46]([CH3:49])([CH3:48])[CH3:47])=[O:34])([CH3:29])([CH3:30])[CH3:31]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 5906793-Acetyl-4,5-dimethyl-1H-pyrrole-2-carboxylic acidHCID 684969241-[2-(2-Amino-2-cyclohexyl-acetylamino)-3,3-dimethyl-butyryl]-octahydro-indole-2-carboxylic acid tert-butyl ester

Product 1

HCID 684929911-(2-{2-[(3-acetyl-4,5-dimethyl-1H-pyrrole-2-carbonyl)-amino]-2-cyclohexyl-acetylamino}-3,3-dimethyl-butyryl)-octahydro-indole-2-carboxylic acid tert-butyl esterYield 85%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

3-acetyl-4,5-dimethyl-2-pyrrole carboxylic acid 10b (2.5 g, 13.7 mmol) in DMF (56 mL) was treated with EDC (2.75 g, 14.4 mmol) and HOBt (2.20 g, 14.4 mmol) and stirred at RT for 15 minutes. Amine 16b (6.23 g, 13.0 mmol) in DMF (10 mL) was added, the reaction mixture stirred at RT and monitored by HPLC. The mixture was concentrated in vacuo, then dissolved in EtOAc. 1.0N glycine sodium salt aqueous solution was added until all excess amino ester 16b was consumed (several hours). The mixture was washed with 1N HCl (3×), brine, bicarb (3×), and brine, then dried over sodium sulfate, filtered, and concentrated in vacuo. Purification through a short plug of silica gel (25%EA/Hex) afforded 7.08 g, (85%) of 1-(2-{2-[(3-acetyl-4,5-dimethyl-1H-pyrrole-2-carbonyl)-amino]-2-cyclohexyl-acetylamino}-3,3-dimethyl-butyryl)-octahydro-indole-2-carboxylic acid tert-butyl ester 17b.

Workup

  1. stirringthe reaction mixture stirred at RT
  2. concentrationThe mixture was concentrated in vacuo
  3. dissolutiondissolved in EtOAc
  4. addition1.0N glycine sodium salt aqueous solution was added until all excess amino ester 16b
  5. customwas consumed (several hours)
  6. washThe mixture was washed with 1N HCl (3×), brine, bicarb (3×), and brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification through a short plug of silica gel (25%EA/Hex)

Sources & evidence

ORD record
ord-f3ff062e77a84ee7b330cbca0ab881eb
Source dataset
uspto-grants-2007_09
Patent number
US07273885B2

Reaction notes

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