Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 2-{5-Chloro-4-[2-fluoro-6-(2-hydroxy-ethoxy)-phenylamino]-pyrimidin-2-ylamino}-5-methyl-8,9-dihydro-5H-7-oxa-5-aza-benzocyclohepten-6-one

HRID 1041710

반응식

HRID 1041710 반응식
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[O:9][CH2:8][CH2:7][C:6]=2[CH:14]=1.Cl[C:16]1[N:21]=[C:20]([NH:22][C:23]2[C:28]([O:29][CH2:30][CH2:31][O:32]C3CCCCO3)=[CH:27][CH:26]=[CH:25][C:24]=2[F:39])[C:19]([Cl:40])=[CH:18][N:17]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C(O)(C)C>[Cl:40][C:19]1[C:20]([NH:22][C:23]2[C:28]([O:29][CH2:30][CH2:31][OH:32])=[CH:27][CH:26]=[CH:25][C:24]=2[F:39])=[N:21][C:16]([NH:1][C:2]2[CH:3]=[CH:4][C:5]3[N:11]([CH3:12])[C:10](=[O:13])[O:9][CH2:8][CH2:7][C:6]=3[CH:14]=2)=[N:17][CH:18]=1

참가 물질

5

반응물 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 58015468HCID 58015468, 화합물HCID 86634071(2,5-Dichloro-pyrimidin-4-yl)-{2-fluoro-6-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-amine

생성물 1

HCID 668298112-{5-Chloro-4-[2-fluoro-6-(2-hydroxy-ethoxy)-phenylamino]-pyrimidin-2-ylamino}-5-methyl-8,9-dihydro-5H-7-oxa-5-aza-benzocyclohepten-6-one수율 10.3%

시약·촉매·용매 1

HCID 3776Isopropanol용매

실험 절차

2-Amino-5-methyl-8,9-dihydro-5H-7-oxa-5-aza-benzocyclohepten-6-one (0.0435 g, 0.000226 mol), (2,5-Dichloro-pyrimidin-4-yl)-{2-fluoro-6-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-amine (0.091 g, 0.00023 mol), 10-Camphorsulfonic acid (0.0788 g, 0.000339 mol), and Isopropyl alcohol (2 mL) were added to a 10 mL microwave tube and microwaved at 120° C. for 30 minutes. The reaction mixture was then purified by HPLC, lyophilized and neutralized with MP-carbonate to afford 2-{5-Chloro-4-[2-fluoro-6-(2-hydroxy-ethoxy)-phenylamino]-pyrimidin-2-ylamino}-5-methyl-8,9-dihydro-5H-7-oxa-5-aza-benzocyclohepten-6-one as a yellow solid (11 mg, 10%). MP=199-201° C.; LCMS: 474 (M+H); HNMR (CDCl3): 8.07 (s, 1H), 7.36 (m, 2H), 7.10 (m, 1H), 6.84 (m, 4H), 6.64 (s, 1H), 4.42 (t, J=7.04 Hz, 2H), 4.13 (m, 2H), 3.87 (m, 2H), 3.33 (s, 3H), 2.78 (t, J=6.32 Hz, 2H).

후처리

  1. custommicrowaved at 120° C. for 30 minutes
  2. customThe reaction mixture was then purified by HPLC

출처 및 근거

ORD 기록
ord-a0ecc83b853846aabee9bd9cfabb63f6
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08552186B2

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