Cesium carbonate → N-(3-(6-((3-fluoro-4-morpholinophenyl)amino)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)acrylamide

HRID 1500791노트

반응식

HRID 1500791 반응식
Cl[C:2]1[N:7]=[C:6]2[N:8]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][O:12]3)[N:9]=[CH:10][C:5]2=[C:4]([C:17]2[CH:18]=[C:19]([NH:23][C:24](=[O:27])[CH:25]=[CH2:26])[CH:20]=[CH:21][CH:22]=2)[N:3]=1.[F:28][C:29]1[CH:30]=[C:31]([CH:33]=[CH:34][C:35]=1[N:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1)[NH2:32].C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:28][C:29]1[CH:30]=[C:31]([NH:32][C:2]2[N:7]=[C:6]3[N:8]([CH:11]4[CH2:16][CH2:15][CH2:14][CH2:13][O:12]4)[N:9]=[CH:10][C:5]3=[C:4]([C:17]3[CH:18]=[C:19]([NH:23][C:24](=[O:27])[CH:25]=[CH2:26])[CH:20]=[CH:21][CH:22]=3)[N:3]=2)[CH:33]=[CH:34][C:35]=1[N:36]1[CH2:37][CH2:38][O:39][CH2:40][CH2:41]1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 14853303-Fluoro-4-morpholinoanilineHCID 86677518N-(3-(6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)acrylamide

생성물 1

HCID 68388393N-(3-(6-((3-fluoro-4-morpholinophenyl)amino)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)acrylamide

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

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온도
200 °C

실험 절차

N-(3-(6-Chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)acrylamide (50 mg, 0.130 mmol), 3-fluoro-4-morpholinoaniline (23.00 mg, 0.117 mmol) and Cs2CO3 (50.9 mg, 0.156 mmol) were dissolved in toluene (5 mL) in a sealable microwave compatible reaction tube, then Pd2(dba)3 (2.386 mg, 2.61 μmol) and Xantphos (3.01 mg, 5.21 μmol) were added. The reaction tube was sealed and the reaction was heated under microwave irradiation (60 min, 200° C., 3 atm). Reaction progress was monitored by TLC. After completion of the reaction, the solvent was removed by vacuum and compound was purified by column chromatography. 1H NMR (400 MHz, CD3OD): δ 8.64 (s, 1H), 8.26 (s, 1H), 7.92 (d, 1H, J=7.6 Hz), 7.82 (dd, 1H, J=2.4 and 15.2 Hz), 7.68 (m, 1H), 7.48 (t, 1H, J=7.6 Hz), 7.35 (dd, 1H, J=1.6 and 8.8 Hz), 6.95 (t, 1H, J=8.8 Hz), 6.43 (m, 2H), 5.87 (dd, 1H, J=2.4 and 10.4 Hz), 5.80 (dd, 1H, J=2.8 and 8.8 Hz), 4.11 (m, 1H), 3.82 (m, 4H), 3.75 (m, 1H), 3.00 (m, 4H), 2.60 (m, 1H), 2.13 (m, 1H), 1.97 (m, 1H), 1.83-1.73 (m, 3H); ESI-MS: [M+H]+.

후처리

  1. customThe reaction tube was sealed
  2. customReaction progress
  3. customAfter completion of the reaction
  4. customthe solvent was removed by vacuum and compound
  5. customwas purified by column chromatography

출처 및 근거

ORD 기록
ord-2fce41c9f5754deb9bfd45af4072096c
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09206176B2

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