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Piperidine → 4-[1-(2-aminopyrimidin-4-yl)-3-methyl-1H-indazol-6-yl]-2-(1,3-oxazol-4-yl)but-3-yn-2-ol

HRID 1398552
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HRID 1398552 반응식
I[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH3:18])=[N:7][N:8]2[C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH2:17])[N:12]=2)=[CH:4][CH:3]=1.N1CCCCC1.[O:25]1[CH:29]=[C:28]([C:30]([OH:34])([C:32]#[CH:33])[CH3:31])[N:27]=[CH:26]1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[NH2:17][C:13]1[N:12]=[C:11]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([C:33]#[C:32][C:30]([C:28]4[N:27]=[CH:26][O:25][CH:29]=4)([OH:34])[CH3:31])[CH:10]=3)[C:6]([CH3:18])=[N:7]2)[CH:16]=[CH:15][N:14]=1
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참가 물질

6

반응물 3

HCID 8082PiperidineHCID 681816364-(6-Iodo-3-methylindazol-1-yl)pyrimidin-2-amineHCID 866695772-(1,3-Oxazol-4-yl)but-3-yn-2-ol

생성물 1

HCID 601651414-[1-(2-aminopyrimidin-4-yl)-3-methyl-1H-indazol-6-yl]-2-(1,3-oxazol-4-yl)but-3-yn-2-ol

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매
HCID 178418397HCID 178418397, 화합물촉매

실험 절차

To a vial was added 4-(6-iodo-3-methylindazol-1-yl)pyrimidin-2-amine (150 mg, 0.43 mmol), piperidine (1.5 mL), tetrakis(triphenylphosphine)palladium (49.36 mg, 0.04 mmol), copper(I) iodide (8.14 mg, 0.04 mmol) and 2-(1,3-oxazol-4-yl)but-3-yn-2-ol (87.87 mg, 0.64 mmol). The mixture was stirred at RT for 20 mins. Reaction mixture was concentrated in vacuo. DCM (5 mL) added and mixture was concentrated in vacuo. This was repeated twice. The crude material was purified by column chromatography (Biotage, 98:2 to 88:12 DCM: methanol gradient). Further purification by flash column chromatography gave the title compound: 1H (500 MHz, DMSO) delta 1.81 (3H, s), 2.58 (3H, s), 6.26 (1H, s), 6.99 (2H, s), 7.04 (1H, d, J=5.5 Hz), 7.39 (1H, dd, J=8.2, 1.1 Hz), 7.85 (1H, d, J=8.1 Hz), 8.13 (1H, s), 8.26 (1H, d, J=5.5 Hz), 8.36 (1H, s), 8.87 (1H, s); LC-MS: m/z=+361.05 (M+H)+.

후처리

  1. customReaction mixture
  2. concentrationwas concentrated in vacuo
  3. additionDCM (5 mL) added
  4. concentrationmixture was concentrated in vacuo
  5. customThe crude material was purified by column chromatography (Biotage, 98:2 to 88:12 DCM: methanol gradient)
  6. customFurther purification by flash column chromatography

출처 및 근거

ORD 기록
ord-a7a66913ddce41cf929e4c3f0c892eb9
출처 데이터셋
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08901313B2

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