4-[6-bromo-3-(fluoromethyl)-1H-indazol-1-yl]pyrimidin-2-amine → 4-[1-(2-aminopyrimidin-4-yl)-3-(fluoromethyl)-1H-indazol-6-yl]-2-(pyrimidin-2-yl)but-3-yn-2-ol

HRID 1398611

반응식

HRID 1398611 반응식
Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:18][F:19])=[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.[N:20]1[CH:25]=[CH:24][CH:23]=[N:22][C:21]=1[C:26]([OH:30])([C:28]#[CH:29])[CH3:27]>N1CCCCC1.C(#N)C.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:29]#[C:28][C:26]([C:21]4[N:20]=[CH:25][CH:24]=[CH:23][N:22]=4)([OH:30])[CH3:27])[CH:10]=3)[C:6]([CH2:18][F:19])=[N:7]2)[CH:16]=[CH:15][N:14]=1

참가 물질

7

반응물 2

HCID 681818784-[6-bromo-3-(fluoromethyl)-1H-indazol-1-yl]pyrimidin-2-amineHCID 866695882-(Pyrimidin-2-yl)but-3-yn-2-ol

생성물 1

HCID 681819214-[1-(2-aminopyrimidin-4-yl)-3-(fluoromethyl)-1H-indazol-6-yl]-2-(pyrimidin-2-yl)but-3-yn-2-ol

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 6342Acetonitrile용매HCID 8082Piperidine용매

반응 조건

온도
66 °C

실험 절차

To a solution of 4-[6-bromo-3-(fluoromethyl)-1H-indazol-1-yl]pyrimidin-2-amine (49 mg, 0.12 mmol) in piperidine (2 mL) was introduced tetrakis(triphenylphosphine)palladium (0) (11.5 mg, 0.01 mmol), copper(I) iodide (1.9 mg, 0.01 mmol) and 2-(pyrimidin-2-yl)but-3-yn-2-ol (39 mg, 0.25 mmol). The reaction mixture was warmed to 66° C. for 2 hr. After cooling to RT, the reaction mixture was concentrated in vacuo, DCM (10 mL) was added and the solution re-evaporated to dryness in vacuo (re-evaporation process repeated twice). Purification of the residue by column chromatography (Biotage, DCM containing a 0-10% gradient of methanol) furnished a brown oil which was suspended in acetonitrile and concentrated in vacuo. The residue was re-suspended in acetonitrile (1 mL), whereupon a brown solid precipitated and was collected by filtration to furnish the title compound as a brown solid: 1H NMR (500 MHz, METHANOL-d4) delta 1.99 (3H, s), 5.75 (2H, d, J=47.92 Hz), 7.23 (1H, d, J=5.36 Hz), 7.42 (1H, dd, J=8.28, 1.02 Hz), 7.48 (1H, t, J=4.89 Hz), 7.85 (1H, d, J=8.20 Hz), 8.25 (1H, d, J=4.73 Hz), 8.88 (2H, d, J=4.89 Hz), 9.06 (1H, s); LC-MS: m/z=+390.05 (M+H)+.

후처리

  1. temperatureAfter cooling to RT
  2. concentrationthe reaction mixture was concentrated in vacuo, DCM (10 mL)
  3. additionwas added
  4. customthe solution re-evaporated to dryness in vacuo (
  5. customre-evaporation process
  6. customPurification of the residue by column chromatography (Biotage, DCM containing a 0-10% gradient of methanol)
  7. customfurnished a brown oil which
  8. concentrationconcentrated in vacuo
  9. customprecipitated
  10. filtrationwas collected by filtration

출처 및 근거

ORD 기록
ord-f1d50df25f7a49c9aa19b5f2f3044f7f
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901313B2

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