Dimethylformamide → 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-oxo-cyclohexyl)-amide

HRID 246144노트

반응식

HRID 246144 반응식
[OH:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH:4]([NH:8][C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:20]4[C:28]5[C:23](=[CH:24][C:25]([Cl:29])=[CH:26][CH:27]=5)[N:22]([CH3:30])[N:21]=4)[N:18]=3)[NH:13][CH:12]=2)=[O:10])[CH2:3]1.ClCCl.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.CN(C=O)C>CCOC(C)=O>[O:1]=[C:2]1[CH2:7][CH2:6][CH2:5][CH:4]([NH:8][C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:20]4[C:28]5[C:23](=[CH:24][C:25]([Cl:29])=[CH:26][CH:27]=5)[N:22]([CH3:30])[N:21]=4)[N:18]=3)[NH:13][CH:12]=2)=[O:10])[CH2:3]1

참가 물질

6

반응물 4

HCID 6228DimethylformamideHCID 6344DichloromethaneHCID 159087TriacetoxyperiodinaneHCID 71287857HCID 71287857, 화합물

생성물 1

HCID 712860002-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-oxo-cyclohexyl)-amide수율 27.3%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

A 25 mL round-bottom flask was charged with 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-hydroxy-cyclohexyl) amide (22 mg, 0.052 mmol) and dichloromethane (5 mL). Dess-Martin periodinane (34.0 mg, 0.08 mmol) was added in one portion to the reaction mixture. The reaction mixture was placed under Ar and stirred for 2 h at room temperature. DMF (1.5 mL) was added and the reaction mixture was stirred for an additional 18 h. The reaction mixture was diluted to 100 mL with EtOAc and washed with sat NaHCO3 (3×20 mL). The crude white precipitate was filtered and reserved. The organic layer was dried over Na2SO4 and concentrated in vacuo to give a crude solid. The combined crude solids were triturated with EtOAc (1×20 mL) then purified by chromatography over SiO2 with MeOH/dichloromethane (gradient: 0%-5% MeOH) to afford 6 mg (27%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-oxo-cyclohexyl)-amide as a white solid. MS: [M+H]+=423, 1H NMR (300 MHz, DMSO-d6) δ: 12.89 (br. s., 1H), 9.09 (s, 1H), 8.47 (s, 1H), 8.42 (d, J=8.7 Hz, 1H), 8.16 (d, J=7.6 Hz, 1H), 8.01 (d, J=1.5 Hz, 1H), 7.39 (dd, J=8.7, 1.9 Hz, 1H), 4.23-4.41 (m, 1H), 4.18 (s, 3H), 2.69-2.78 (m, 1H), 2.58 (d, J=10.2 Hz, 1H), 2.42 (dd, J=11.1, 5.9 Hz, 1H), 2.17-2.34 (m, 2H), 1.96-2.08 (m, 1H), 1.80-1.93 (m, 1H), 1.65-1.80 (m, 1H).

후처리

  1. stirringthe reaction mixture was stirred for an additional 18 h
  2. washwashed
  3. filtrationThe crude white precipitate was filtered
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customto give a crude solid
  7. customwere triturated with EtOAc (1×20 mL)
  8. customthen purified by chromatography over SiO2 with MeOH/dichloromethane (gradient: 0%-5% MeOH)

출처 및 근거

ORD 기록
ord-dba74c3c1c5e4106a59a787103c534da
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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