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Dimethylformamide → 4-[8-Chloro-1-(2-phenyl-quinolin-7-yl)-imidazo[1,5-a]pyrazin-3-yl]-piperidine-1-carboxylic acid benzyl ester

HRID 422621
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HRID 422621 반응식
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17](=O)[NH:18][CH:19]([C:36]2[C:41]([Cl:42])=[N:40][CH:39]=[CH:38][N:37]=2)[C:20]2[CH:29]=[C:28]3[C:23]([CH:24]=[CH:25][C:26]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[N:27]3)=[CH:22][CH:21]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C=O)C.O=P(Cl)(Cl)Cl>CC#N>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][CH:14]([C:17]2[N:37]3[CH:38]=[CH:39][N:40]=[C:41]([Cl:42])[C:36]3=[C:19]([C:20]3[CH:29]=[C:28]4[C:23]([CH:24]=[CH:25][C:26]([C:30]5[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=5)=[N:27]4)=[CH:22][CH:21]=3)[N:18]=2)[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 576810294-{[(3-Chloro-pyrazin-2-yl)-(2-phenyl-quinolin-7-yl)-methyl]carbamoyl}-piperidine-1-carboxylic acid benzyl ester

생성물 1

HCID 536290294-[8-Chloro-1-(2-phenyl-quinolin-7-yl)-imidazo[1,5-a]pyrazin-3-yl]-piperidine-1-carboxylic acid benzyl ester

시약·촉매·용매 1

HCID 6342
Acetonitrile
용매

반응 조건

온도
55 °C

실험 절차

4-{[(3-Chloro-pyrazin-2-yl)-(2-phenyl-quinolin-7-yl)-methyl]-carbamoyl}-piperidine-1-carboxylic acid benzyl ester (2.1 g, 3.6 mmol) was dissolved in CH3CN (126.0 mL) and DMF (0.4 mL) in a round bottom flask equipped with a condenser. The reaction was charged with POCl3 (1.7 mL, 17.9 mmol) and stirred at 55° C. for 3 h. The reaction mixture was concentrated in vacuo, redissolved in DCM, cooled to 0° C., and charged with 2M NH3 in isopropanol to basic pH. Hydromatrix was added, the mixture was concentrated in vacuo, and the resulting residue was purified by silica gel chromatography (Jones Flashmaster, 20 g/70 mL cartridge, eluting with 100% CH2Cl2 to 2% CH3CN/CH2Cl2) to afford 4-[8-chloro-1-(2-phenyl-quinolin-7-yl)-imidazo[1,5-a]pyrazin-3-yl]-piperidine-1-carboxylic acid benzyl ester as a yellow solid; MS (ES+): m/z 574 (100) [MH+]; HPLC: tR=4.2 min (OpenLynx, polar—5 min).

후처리

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionredissolved in DCM
  3. temperaturecooled to 0° C.
  4. additioncharged with 2M NH3 in isopropanol to basic pH
  5. additionHydromatrix was added
  6. concentrationthe mixture was concentrated in vacuo
  7. customthe resulting residue was purified by silica gel chromatography (Jones Flashmaster, 20 g/70 mL cartridge, eluting with 100% CH2Cl2 to 2% CH3CN/CH2Cl2)

출처 및 근거

ORD 기록
ord-131c061f9b86477d9ae8af8e3be93888
출처 데이터셋
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08101613B2

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