Water → {(S)-2-[(S)-5-(6-Chloro-9H-beta-carbolin-8-ylcarbamoyl)-2,2-dimethyl-morpholin-4-yl]-1-methyl-ethyl]-carbamic acid methyl ester

HRID 12227Notes

Reaction equation

HRID 12227 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]2[C:13](=[C:14]([NH:16][C:17]([C@@H:19]3[CH2:24][O:23][C:22]([CH3:26])([CH3:25])[CH2:21][N:20]3[CH2:27][C@@H:28]([NH2:30])[CH3:29])=[O:18])[CH:15]=1)[NH:12][C:11]1[CH:10]=[N:9][CH:8]=[CH:7][C:6]2=1.C(Cl)Cl.Cl[C:35]([O:37][CH3:38])=[O:36].O>N1C=CC=CC=1>[CH3:38][O:37][C:35](=[O:36])[NH:30][C@@H:28]([CH3:29])[CH2:27][N:20]1[C@H:19]([C:17](=[O:18])[NH:16][C:14]2[CH:15]=[C:3]([Cl:2])[CH:4]=[C:5]3[C:13]=2[NH:12][C:11]2[CH:10]=[N:9][CH:8]=[CH:7][C:6]3=2)[CH2:24][O:23][C:22]([CH3:25])([CH3:26])[CH2:21]1

Participants

6

Reactant 4

HCID 962WaterHCID 6344DichloromethaneHCID 6586Methyl chloroformateHCID 67165873HCID 67165873, compound

Product 1

HCID 11271436{(S)-2-[(S)-5-(6-Chloro-9H-beta-carbolin-8-ylcarbamoyl)-2,2-dimethyl-morpholin-4-yl]-1-methyl-ethyl]-carbamic acid methyl esterYield 77%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of (S)-4-((S)-2-Amino-propyl)-6,6-dimethyl-morpholine-3 carboxylic acid (6-chloro-9H-beta-carbolin-8-yl)-amide hydrochloride salt (3.45 g, 6.59 mmole) in 68 ml of dry pyridine, was added in three portions over 1.5 hr, a 3M DCM solution of methyl chloroformate (9.2 ml, 27.6 mmole, 4.2 eq). After 2 h, 10 ml of water were added and the mixture was concentrated to dryness. The residue was partitioned into 150 ml Of EtOAc and 100 ml of an aqueous 0.5M solution of K2CO3. The separated aqueous phase was extracted with 50 ml of EtOAc. The combined organic extracts were successively washed with water (2×50 ml) and brine (50 ml), dried over Na2SO4 and concentrated to dryness. The residue was purified on silica (5% MeOH/CH2Cl2) to give 2.48 g(thick oil, 77% yield) of the desired product.

Workup

  1. concentrationthe mixture was concentrated to dryness
  2. customThe residue was partitioned into 150 ml Of EtOAc and 100 ml of an aqueous 0.5M solution of K2CO3
  3. extractionThe separated aqueous phase was extracted with 50 ml of EtOAc
  4. washThe combined organic extracts were successively washed with water (2×50 ml) and brine (50 ml)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to dryness
  7. customThe residue was purified on silica (5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-511991e8196149f8bbc6a6fd32b06b34
Source dataset
uspto-grants-2010_06
Patent number
US07727985B2

Reaction notes

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