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Ammonia → (S)-N-(6-aminopyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide

HRID 1485322
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HRID 1485322 반응식
F[C:2]1[N:7]=[CH:6][C:5]([NH:8][C:9]([C@@H:11]2[CH2:15][CH2:14][CH2:13][N:12]2[C:16]2[N:17]=[C:18]([NH:25][C:26]3[CH:30]=[C:29]([CH:31]([CH3:33])[CH3:32])[NH:28][N:27]=3)[C:19]3[CH2:24][CH2:23][CH2:22][C:20]=3[N:21]=2)=[O:10])=[CH:4][CH:3]=1.[NH3:34]>O1CCOCC1>[NH2:34][C:2]1[N:7]=[CH:6][C:5]([NH:8][C:9]([C@@H:11]2[CH2:15][CH2:14][CH2:13][N:12]2[C:16]2[N:17]=[C:18]([NH:25][C:26]3[CH:30]=[C:29]([CH:31]([CH3:33])[CH3:32])[NH:28][N:27]=3)[C:19]3[CH2:24][CH2:23][CH2:22][C:20]=3[N:21]=2)=[O:10])=[CH:4][CH:3]=1
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참가 물질

4

반응물 2

HCID 222AmmoniaHCID 76072890(S)-N-(6-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide

생성물 1

HCID 86723665(S)-N-(6-aminopyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

실험 절차

To a solution of (S)—N-(6-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide (250 mg, 0.55 mmol) in 1,4-dioxane (5 mL) was added aqueous ammonia (5 mL) and the reaction mixture was allowed to reflux in steel bomb at 130° C. for 18 h. The reaction mixture was concentrated under vacuum to obtain an oily crude product which was purified by reverse phase HPLC to afford 8 mg of (S)—N-(6-aminopyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide. 1H NMR (400 MHz, CD3OD, freebase) δ (ppm): 1.20 (d, 6H), 2.00-2.20 (m, 4H), 2.75-2.95 (m, 5H), 3.50-3.90 (m, 4H), 4.90-4.98 (m, 1H), 6.40 (s, 1H), 6.50 (d, 1H), 7.40 (s, 1H), 7.90 (s, 1H). The other enantiomer is prepared using the chiral (R) starting material.

후처리

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. customto obtain an oily crude product which
  3. customwas purified by reverse phase HPLC

출처 및 근거

ORD 기록
ord-204eb080c785498a861a23fbd13d9019
출처 데이터셋
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09422267B2

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