Ammonium Chloride → 4-[(3aR,6aR)-5-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,2-c]pyrrol-1-yl]-N-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-6-methoxybenzene-1,3-diamine

HRID 1842698

반응식

HRID 1842698 반응식
[CH3:1][N:2]1[CH2:6][C@@H:5]2[N:7]([C:10]3[C:15]([N+:16]([O-])=O)=[CH:14][C:13]([NH:19][C:20]4[N:25]=[C:24]([C:26]5[CH:27]=[N:28][N:29]6[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=56)[C:23]([Cl:35])=[CH:22][N:21]=4)=[C:12]([O:36][CH3:37])[CH:11]=3)[CH2:8][CH2:9][C@@H:4]2[CH2:3]1.[NH4+].[Cl-]>C(O)C.O.[Fe]>[CH3:1][N:2]1[CH2:6][C@@H:5]2[N:7]([C:10]3[CH:11]=[C:12]([O:36][CH3:37])[C:13]([NH:19][C:20]4[N:25]=[C:24]([C:26]5[CH:27]=[N:28][N:29]6[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=56)[C:23]([Cl:35])=[CH:22][N:21]=4)=[CH:14][C:15]=3[NH2:16])[CH2:8][CH2:9][C@@H:4]2[CH2:3]1

참가 물질

6

반응물 2

HCID 25517Ammonium ChlorideHCID 71270223N-[4-[(3aR,6aR)-5-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,2-c]pyrrol-1-yl]-2-methoxy-5-nitrophenyl]-5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine2회

생성물 1

HCID 866772374-[(3aR,6aR)-5-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,2-c]pyrrol-1-yl]-N-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-6-methoxybenzene-1,3-diamine수율 72%

시약·촉매·용매 3

HCID 23925Iron촉매HCID 702Ethanol용매HCID 962Water용매

실험 절차

A mixture of N-[4-[(3aR,6aR)-5-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,2-c]pyrrol-1-yl]-2-methoxy-5-nitrophenyl]-5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 36, 155 mg, 0.30 mmol), iron (100 mg, 1.79 mmol) and NH4Cl (11.2 mg, 0.21 mmol) in ethanol (12 mL) and water (4 mL) was heated at reflux for 2 h. The mixture was then cooled and filtered though decalite (a type of diatomaceous earth) and the filtrate was concentrated in vacuo to provide a brown gum. Purification by FCC, eluting with 0-5% 7N methanolic ammonia in CH2Cl2 gave the title compound (105 mg, 72%) as a gum; 1H NMR: (CDCl3) 1.76-1.80 (1H, m), 2.03-2.20 (2H, m), 2.28 (3H, s), 2.48 (1H, dd), 2.59-2.63 (2H, m), 2.76-2.98 (2H, m), 3.46 (1H, dt), 3.78 (2H, s), 3.84 (3H, s), 4.07-4.10 (1H, m), 6.73 (1H, s), 6.94 (1H, td), 7.36 (1H, ddd), 7.51 (1H, s), 7.86 (1H, s), 8.35 (1H, s), 8.54 (1H, d), 8.65 (1H, d), 8.93 (1H, s); m/z: ES+ MH+ 491.29.

후처리

  1. temperaturewas heated
  2. temperatureat reflux for 2 h
  3. temperatureThe mixture was then cooled
  4. filtrationfiltered though decalite (a type of diatomaceous earth) and the filtrate
  5. concentrationwas concentrated in vacuo
  6. customto provide a brown gum
  7. customPurification by FCC
  8. washeluting with 0-5% 7N methanolic ammonia in CH2Cl2

출처 및 근거

ORD 기록
ord-69c106480d7449baa1c8cdf706abab79
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946235B2

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