Water → 4-[(3aR,6aR)-5-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,4-b]pyrrol-1-yl]-6-methoxy-N-[4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,3-diamine

HRID 1842777

반응식

HRID 1842777 반응식
[CH3:1][N:2]1[CH2:9][C@@H:8]2[C@@H:4]([N:5]([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[C:34]6[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=6)[N:28]([CH3:35])[CH:27]=5)[CH:23]=[CH:22][N:21]=4)=[C:12]([O:36][CH3:37])[CH:11]=3)[CH2:6][CH2:7]2)[CH2:3]1.[NH4+].[Cl-].O>C(O)C.[Fe]>[CH3:1][N:2]1[CH2:9][C@@H:8]2[C@@H:4]([N:5]([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[C:34]6[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=6)[N:28]([CH3:35])[CH:27]=5)[CH:23]=[CH:22][N:21]=4)=[CH:14][C:15]=3[NH2:16])[CH2:6][CH2:7]2)[CH2:3]1

참가 물질

6

반응물 3

HCID 962WaterHCID 25517Ammonium ChlorideHCID 71269801N-[4-[(3aR,6aR)-5-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,4-b]pyrrol-1-yl]-2-methoxy-5-nitrophenyl]-4-(1-methylindol-3-yl)pyrimidin-2-amine2회

생성물 1

HCID 866772894-[(3aR,6aR)-5-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,4-b]pyrrol-1-yl]-6-methoxy-N-[4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,3-diamine수율 82.7%

시약·촉매·용매 2

HCID 23925Iron촉매HCID 702Ethanol용매

실험 절차

A mixture of N-[4-[(3aR,6aR)-5-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,4-b]pyrrol-1-yl]-2-methoxy-5-nitrophenyl]-4-(1-methylindol-3-yl)pyrimidin-2-amine (Intermediate 124, 256 mg, 0.51 mmol), iron powder (172 mg, 3.07 mmol) and NH4Cl (19.19 mg, 0.36 mmol) were heated in ethanol (3 mL) and water (1 mL) at reflux for 18 h. The crude mixture was then purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M methanolic ammonia and concentrated in vacuo. Further purification by FCC, eluting with 0-5% 7N methanolic ammonia in CH2Cl2 gave the title compound (198 mg, 82%) as a yellow foam; 1H NMR (CDCl3) 1.78 (1H, td), 2.07-2.13 (1H, m), 2.15 (1H, dd), 2.29 (3H, s), 2.47 (1H, dd), 2.57-2.65 (2H, m), 2.82-2.95 (2H, m), 3.45 (1H, dt), 3.85 (3H, s), 3.88 (3H, s), 4.07 (1H, ddd), 6.74 (1H, s), 7.01 (1H, d), 7.27-7.35 (2H, m), 7.38 (1H, dd), 7.55 (1H, s), 7.79 (1H, s), 8.14 (1H, s), 8.33 (1H, d), 8.45-8.52 (1H, m); m/z: ES+ MH+ 470.29.

후처리

  1. customThe crude mixture was then purified by ion exchange chromatography
  2. washThe desired product was eluted from the column
  3. concentrationconcentrated in vacuo
  4. customFurther purification by FCC
  5. washeluting with 0-5% 7N methanolic ammonia in CH2Cl2

출처 및 근거

ORD 기록
ord-457fae03f77348ac860810ec17377bf9
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946235B2

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