7-Amino-1,1-dimethyl-1,2,4,5-tetrahydrobenzo[c]azepin-3-one → 2-(2-(3-(3-amino-3-oxopropyl)-4-(prop-1-en-2-yl)phenylamino)-5-chloropyrimidin-4-ylamino)-3-fluoro-N-methylbenzamide

HRID 1688117노트

반응식

HRID 1688117 반응식
[NH2:1][C:2]1[CH:15]=[CH:14][C:5]2[C:6]([CH3:13])([CH3:12])[NH:7][C:8](=[O:11])[CH2:9][CH2:10][C:4]=2[CH:3]=1.Cl[C:17]1[N:22]=[C:21]([NH:23][C:24]2[C:33]([F:34])=[CH:32][CH:31]=[CH:30][C:25]=2[C:26]([NH:28][CH3:29])=[O:27])[C:20]([Cl:35])=[CH:19][N:18]=1>Cl.O1CCOCC1.CC(O)C>[NH2:7][C:8](=[O:11])[CH2:9][CH2:10][C:4]1[CH:3]=[C:2]([NH:1][C:17]2[N:22]=[C:21]([NH:23][C:24]3[C:33]([F:34])=[CH:32][CH:31]=[CH:30][C:25]=3[C:26]([NH:28][CH3:29])=[O:27])[C:20]([Cl:35])=[CH:19][N:18]=2)[CH:15]=[CH:14][C:5]=1[C:6]([CH3:13])=[CH2:12]

참가 물질

5

반응물 2

HCID 672644267-Amino-1,1-dimethyl-1,2,4,5-tetrahydrobenzo[c]azepin-3-oneHCID 717421912-(2,5-Dichloropyrimidin-4-ylamino)-3-fluoro-N-methyl-benzamide

생성물 1

HCID 672643982-(2-(3-(3-amino-3-oxopropyl)-4-(prop-1-en-2-yl)phenylamino)-5-chloropyrimidin-4-ylamino)-3-fluoro-N-methylbenzamide

시약·촉매·용매 2

HCID 204431481,4-Dioxane hydrochloride촉매HCID 3776Isopropanol용매

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온도
120 °C

실험 절차

A mixture of 7-amino-1,1-dimethyl-1,2,4,5-tetrahydrobenzo[c]azepin-3-one (40 mg), 2-(2,5-dichloropyrimidin-4-ylamino)-3-fluoro-N-methylbenzamide (50 mg), and 2 drops of 4 N HCl/dioxane in IPA (3 mL) were microwave-heated at 120° C. for 1.5 hours. The mixture was concentrated to afford crude 2-(2-(3-(3-amino-3-oxopropyl)-4-(prop-1-en-2-yl)phenylamino)-5-chloropyrimidin-4-ylamino)-3-fluoro-N-methylbenzamide. The crude mixture was stirred for 4 hours in TFA and concentrated. Purification by semi-preparative HPLC provided 2-(5-chloro-2-(1,1-dimethyl-3-oxo-2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-ylamino)pyrimidin-4-ylamino)-3-fluoro-N-methylbenzamide (45.7 mg) as a TFA salt: 1H NMR (300 MHz, CD3OD) δ 8.3 (s, 1H), 7.7-7.5 (m, 3H), 7.65 (s, 1H, slowly exchanging NH), 7.4 (d, 1H), 7.32 (d, 1H), 7.28 (dd, 1H), 3.0 (m, 2H), 3.0 (s, 3H), 2.7 (m, 2H), 1.8 (s, 6H).

후처리

  1. concentrationThe mixture was concentrated

출처 및 근거

ORD 기록
ord-0cd97495e40742ff999713f7f6a57cd5
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08148391B2

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