Sodium hydride → {3-[3-(2-cyano-benzyl)-5-methyl-4-oxo-4,5-dihydro-3H-1,3,5,6-tetraaza-cyclopenta[a]naphthalen-2-yl]-cyclohexyl}-carbamic acid benzyl ester

HRID 2244814노트

반응식

HRID 2244814 반응식
[CH2:1]([O:8][C:9](=[O:32])[NH:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH:13]([C:17]2[NH:18][C:19]3[C:28](=[O:29])[N:27]([CH3:30])[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][N:25]=4)[C:20]=3[N:31]=2)[CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[H][H].[C:37]([C:39]1[CH:46]=[CH:45][CH:44]=[CH:43][C:40]=1[CH2:41]Br)#[N:38]>CN(C=O)C>[CH2:1]([O:8][C:9](=[O:32])[NH:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH:13]([C:17]2[N:18]([CH2:41][C:40]3[CH:43]=[CH:44][CH:45]=[CH:46][C:39]=3[C:37]#[N:38])[C:19]3[C:28](=[O:29])[N:27]([CH3:30])[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][N:25]=4)[C:20]=3[N:31]=2)[CH2:12]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

참가 물질

6

반응물 4

HCID 24758Sodium hydrideHCID 895992-(Bromomethyl)benzonitrileHCID 58788434[3-(5-methyl-4-oxo-4,5-dihydro-3H-1,3,5,6-tetraaza-cyclopenta[a]naphthalen-2-yl)-cyclohexyl]-carbamic acid benzyl esterHCID 178418361HCID 178418361, 화합물

생성물 1

HCID 16045626{3-[3-(2-cyano-benzyl)-5-methyl-4-oxo-4,5-dihydro-3H-1,3,5,6-tetraaza-cyclopenta[a]naphthalen-2-yl]-cyclohexyl}-carbamic acid benzyl ester수율 100,618.5%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of [3-(5-methyl-4-oxo-4,5-dihydro-3H-1,3,5,6-tetraaza-cyclopenta[a]naphthalen-2-yl)-cyclohexyl]-carbamic acid benzyl ester (45 mg, 0.10 μmol) in DMF (2 mL) was added NaH (5 mg, 0.12 mmol 60% in mineral oil) at 0° C. After hydrogen evolution had ceased, 2-cyanobenzylbromide (31 mg, 0.16 mmol) was added and the reaction was stirred at room temperature for 2 h. The flask was cooled with an ice-bath, and the reaction was quenched by addition of saturated aqueous NH4Cl. The mixture was extracted with CH2Cl2 and the organics were dried over MgSO4 and concentrated in vacuo. The crude product was purified by flash chromatography, eluting with 1% MeOH to give {3-[3-(2-cyano-benzyl)-5-methyl-4-oxo-4,5-dihydro-3H-1,3,5,6-tetraaza-cyclopenta[a]naphthalen-2-yl]-cyclohexyl}-carbamic acid benzyl ester (55 mg, 97% yield). 1H-NMR (CDCl3): δ 8.58 (m, 2H), 7.75 (m, 1H), 7.48 (m, 1H), 7.35 (m, 6H), 7.17 (d, 1H, J=7.6 Hz), 6.26 (m, 1H), 5.96 (m, 1H), 5.08 (s, 2H), 3.91 (s, 3H), 3.69 (m, 1H), 2.93 (m, 1H), 2.08 (m, 1H), 1.98 (m, 1H), 1.83 (m, 2H), 1.76 (m, 1H), 1.59 (m, 1H), 1.51 (m, 1H), 1.33 (m, 1H). MS: calculated for C32H30N6O3+H 547.3; found: 547.2.

후처리

  1. temperatureThe flask was cooled with an ice-bath
  2. customthe reaction was quenched by addition of saturated aqueous NH4Cl
  3. extractionThe mixture was extracted with CH2Cl2
  4. dry with materialthe organics were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography
  7. washeluting with 1% MeOH

출처 및 근거

ORD 기록
ord-0a97bb0995b04506ad2a4e77e6725069
출처 데이터셋
uspto-grants-2010_03
특허 번호
US07678909B1

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