(3R)-(+)-3-Acetamidopyrrolidine → (R)-N-(7-(3-acetamidopyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

HRID 1256392

반응식

HRID 1256392 반응식
Cl[C:2]1[N:7]2[N:8]=[C:9](C)[CH:10]=[C:6]2[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]2[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)[CH:3]=1.[NH:25]1[CH2:29][CH2:28][C@@H:27]([NH:30][C:31](=[O:33])[CH3:32])[CH2:26]1>CN1C(=O)CCC1>[C:31]([NH:30][C@@H:27]1[CH2:28][CH2:29][N:25]([C:2]2[N:7]3[N:8]=[CH:9][CH:10]=[C:6]3[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]3[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:21])[CH3:22])=[CH:16][CH:15]=3)[CH:3]=2)[CH2:26]1)(=[O:33])[CH3:32]

참가 물질

4

반응물 2

HCID 7016129(3R)-(+)-3-AcetamidopyrrolidineHCID 86652267N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

생성물 1

HCID 67064162(R)-N-(7-(3-acetamidopyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide수율 108.5%

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

In a 2 mL microwave vial were placed N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2D, 80 mg, 0.24 mmol) and (R)-N-(pyrrolidin-3-yl)acetamide (62 mg, 0.48 mmol). To the sealed vial were then added NMP (2 ml), and the mixture was then heated in the microwave at 100° C. for 15 minutes. After cooling to room temperature, the reaction mixture was filtered by syringe filter and was then directly purified by preparatory HPLC (20-40% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a white powder (110 mg, 99% yield). 1H NMR (400 MHz, DMSO-d6) δ=10.84 (s, 1 H), 8.24 (d, J=6.3 Hz, 1 H), 8.01 (d, J=2.3 Hz, 1 H), 8.00-7.95 (m, 2 H), 7.65-7.59 (m, 2 H), 6.90 (s, 1 H), 6.28 (d, J=2.3 Hz, 1 H), 4.41-4.31 (m, 1H), 4.19 (br. s., 1 H), 3.96 (br. s., 2 H), 2.19 (dd, J=5.8, 12.6 Hz, 1 H), 2.01-1.91 (m, 1 H), 1.83 (s, 3 H), 1.46 (s, 6 H); ESI-MS: m/z 423.4 (M+H)+.

후처리

  1. filtrationthe reaction mixture was filtered by syringe
  2. filtrationfilter
  3. customwas then directly purified by preparatory HPLC (20-40% MeCN/H2O gradient+0.01% TFA)

출처 및 근거

ORD 기록
ord-697d596f865f460b991457cacb45d461
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08461163B2

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