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

反応式

HRID 1842698 の反応式
[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

参加物

6

反応物 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-amine2 回

生成物 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-diamine収率 72%

試薬・触媒・溶媒 3

HCID 23925Iron触媒HCID 702Ethanol溶媒HCID 962Water溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-69c106480d7449baa1c8cdf706abab79
出典データセット
uspto-grants-2015_02
特許番号
US08946235B2

関連ノート

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