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 552229노트

반응식

HRID 552229 반응식
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

참가 물질

6

반응물 4

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

생성물 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 ester수율 77%

시약·촉매·용매 1

HCID 1049Pyridine용매

실험 절차

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 1H-NMR (300 MHz, CDCl3): δ 1.15 (d, 3H), 1.28 (s, 3H), 1.42 (s, 3H), 2.33 (dd, 1H), 2.42 (d, 1H), 2.78 (dd, 1H), 2.86 (d, 1H), 3.32 (dd, 1H), 3.86 (s, 3H), 3.92 (t, 1H), 4.01 (dd, 1H), 4.18 (m, 1H), 4.78 (d, 1H), 7.95 (d, 1H), 7.97 (s, 1H), 8.29 (s, 1H), 8.50 (d, 1H), 8.98 (s, 1H), 9.88 (s, 1H), 10.94 (s, 1H). Retention Time (LC, method: ammonium acetate standard): 1.70 min. MS (M+H+): 474.1

후처리

  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)

출처 및 근거

ORD 기록
ord-c94faff7a14d4e0b80b47a43020f99ec
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07951801B2

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