Piperidine → 1-[2-amino-6-(methylamino)pyrimidin-4-yl]-6-[3-hydroxy-3-(pyrimidin-2-yl)but-1-yn-1-yl]-N,N-dimethyl-1H-indazole-3-carboxamide

HRID 1398624

반응식

HRID 1398624 반응식
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14](I)[CH:15]=3)[C:10]([C:18]([N:20]([CH3:22])[CH3:21])=[O:19])=[N:9]2)[CH:5]=[C:4]([NH:23][CH3:24])[N:3]=1.N1CCCCC1.[N:31]1[CH:36]=[CH:35][CH:34]=[N:33][C:32]=1[C:37]([OH:41])([C:39]#[CH:40])[CH3:38]>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.C(OCC)(=O)C.CCCCCCC>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:40]#[C:39][C:37]([OH:41])([C:32]4[N:33]=[CH:34][CH:35]=[CH:36][N:31]=4)[CH3:38])[CH:15]=3)[C:10]([C:18]([N:20]([CH3:22])[CH3:21])=[O:19])=[N:9]2)[CH:5]=[C:4]([NH:23][CH3:24])[N:3]=1

참가 물질

7

반응물 3

HCID 8082PiperidineHCID 681818081-[2-amino-6-(methylamino)pyrimidin-4-yl]-6-iodo-N,N-dimethyl-1H-indazole-3-carboxamideHCID 866695882-(Pyrimidin-2-yl)but-3-yn-2-ol

생성물 1

HCID 681816351-[2-amino-6-(methylamino)pyrimidin-4-yl]-6-[3-hydroxy-3-(pyrimidin-2-yl)but-1-yn-1-yl]-N,N-dimethyl-1H-indazole-3-carboxamide

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 21899848Ethylacetate heptane용매

실험 절차

To a sealed tube was added 1-[2-amino-6-(methylamino)pyrimidin-4-yl]-6-iodo-N,N-dimethyl-1H-indazole-3-carboxamide (86 mg, 0.20 mmol), followed by piperidine (2 mL), tetrakis(triphenylphosphine)palladium (23 mg, 0.02 mmol), copper(I) iodide (4 mg, 0.02 mmol) and 2-(pyrimidin-2-yl)but-3-yn-2-ol (58 mg, 0.39 mmol). The reaction mixture was purged with nitrogen gas, capped and stirred at room temperature for 1.5 hr. After cooling to RT, the reaction mixture was concentrated in vacuo. EtOAc (5 mL) was added and concentration in vacuo repeated. The residue was purified using column chromatography (Biotage, 0-10% gradient of methanol in DCM) to give a brown solid. Trituration of the solid with ethyl acetate/heptane gave the title compound. 1H NMR (DMSO, 500 MHz) delta 1.92 (3H, s), 2.80 (3H, d, J=4.1 Hz), 3.10 (3H, s), 3.31 (3H, s), 6.26 (2H, s), 6.49 (2H, s), 7.11 (1H, s), 7.30 (1H, d, J=8.4 Hz), 7.51 (1H, t, J=4.9 Hz), 7.94 (1H, d, J=8.4 Hz), 8.78-9.04 (3H, m); LC-MS: m/z=+458.10 (M+H)+.

후처리

  1. customThe reaction mixture was purged with nitrogen gas
  2. customcapped
  3. temperatureAfter cooling to RT
  4. concentrationthe reaction mixture was concentrated in vacuo
  5. additionEtOAc (5 mL) was added
  6. concentrationconcentration in vacuo
  7. customThe residue was purified
  8. customto give a brown solid

출처 및 근거

ORD 기록
ord-e2ccff1fe8d440c99e4783d043d88a78
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901313B2

연결된 노트

불러오는 중…