Lithium Hexamethyldisilazide → N-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-yl)-1-chloro-6-methylisoquinolin-5-amine

HRID 1042270

반응식

HRID 1042270 반응식
F[C:2]1[C:7]([C:8]2[C:9]3[CH:16]=[CH:15][NH:14][C:10]=3[N:11]=[CH:12][N:13]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[Cl:17][C:18]1[C:27]2[CH:26]=[CH:25][C:24]([CH3:28])=[C:23]([NH2:29])[C:22]=2[CH:21]=[CH:20][N:19]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[N:11]1[C:10]2[NH:14][CH:15]=[CH:16][C:9]=2[C:8]([C:7]2[C:2]([NH:29][C:23]3[C:22]4[CH:21]=[CH:20][N:19]=[C:18]([Cl:17])[C:27]=4[CH:26]=[CH:25][C:24]=3[CH3:28])=[N:3][CH:4]=[CH:5][CH:6]=2)=[N:13][CH:12]=1

참가 물질

5

반응물 3

HCID 2733832Lithium HexamethyldisilazideHCID 59627370HCID 59627370, 화합물HCID 596273751-Chloro-6-methylisoquinolin-5-amine

생성물 1

HCID 59627376N-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-yl)-1-chloro-6-methylisoquinolin-5-amine수율 73%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
22 °C

실험 절차

A mixture of 4-(2-fluoropyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (2.17 g, 10.1 mmol) and 1-chloro-6-methylisoquinolin-5-amine (1.95 g, 10.1 mmol) in THF (4 mL) was sonicated for 3 min until throughly mixed. Lithium bis(trimethylsilyl)amide (7.63 g, 45.6 mmol) (1 N in THF from Aldrich) was added in a stream and the resulting dark brown solution was stirred at 22° C. for 4 h. The reaction was quenched with NaHCO3 (aq., sat.) while cooled in an ice bath. The reaction mixture was then partitioned between EtOAc and NaHCO3 (aq., sat). The aqueous layer was washed with EtOAc twice. The organic layers were combined and concentrated in vacuo. The light brown solid residue was triturated with EtOAc (˜50 mL) to give a yellow solid. This solid was collected by filtration and washed with EtOAc twice and then dried in a vacuum oven (45° C.) over the weekend to give N-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-yl)-1-chloro-6-methylisoquinolin-5-amine as a yellow solid (2.85 g, 73% yield). MS (ESI, pos. ion) m/z: 387 [M+H]+

후처리

  1. customwas sonicated for 3 min
  2. additionuntil throughly mixed
  3. customThe reaction was quenched with NaHCO3 (aq., sat.)
  4. temperaturewhile cooled in an ice bath
  5. customThe reaction mixture was then partitioned between EtOAc and NaHCO3 (aq., sat)
  6. washThe aqueous layer was washed with EtOAc twice
  7. concentrationconcentrated in vacuo
  8. customThe light brown solid residue was triturated with EtOAc (˜50 mL)
  9. customto give a yellow solid
  10. filtrationThis solid was collected by filtration
  11. washwashed with EtOAc twice
  12. customdried in a vacuum oven (45° C.) over the weekend

출처 및 근거

ORD 기록
ord-f4bc954ff6e34216b22f4b38b2c0bbc1
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08557830B2

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