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Ammonium Chloride → 4-[(3aR,6aR)-5-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,4-b]pyrrol-1-yl]-6-methoxy-N-[4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamine

HRID 1842785
ノート
印刷プレビュー

反応式

HRID 1842785 の反応式
[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[CH:27]=[N:28][N:29]6[CH2:34][CH2:33][CH2:32][CH2:31][C:30]=56)[CH:23]=[CH:22][N:21]=4)=[C:12]([O:35][CH3:36])[CH:11]=3)[CH2:6][CH2:7]2)[CH2:3]1.[NH4+].[Cl-]>C(O)C.O.[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:35][CH3:36])[C:13]([NH:19][C:20]4[N:25]=[C:24]([C:26]5[CH:27]=[N:28][N:29]6[CH2:34][CH2:33][CH2:32][CH2:31][C:30]=56)[CH:23]=[CH:22][N:21]=4)=[CH:14][C:15]=3[NH2:16])[CH2:6][CH2:7]2)[CH2:3]1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 2

HCID 25517Ammonium ChlorideHCID 71269945N-{4-[(3aR,6aR)-5-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,4-b]pyrrol-1-yl]-2-methoxy-5-nitrophenyl}-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine2 回

生成物 1

HCID 866772934-[(3aR,6aR)-5-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,4-b]pyrrol-1-yl]-6-methoxy-N-[4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamine収率 33%

試薬・触媒・溶媒 3

HCID 23925
Iron
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[3,4-b]pyrrol-1-yl]-2-methoxy-5-nitrophenyl}-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine (Intermediate 133, 400 mg, 0.82 mmol), iron (273 mg, 4.89 mmol) and NH4Cl (30.5 mg, 0.57 mmol) in ethanol (12 mL) and water (4 mL) was heated at reflux for 4 h and then stirred at r.t.overnight. Part-purification by ion exchange chromatography, using an SCX column, eluting with 7M methanolic ammonia provided crude material that was concentrated in vacuo onto silica. Purification by FCC, eluting with 0-5% 7N methanolic ammonia in CH2Cl2 provided impure product as a brown gum. Further purification by FCC, eluting with 0-2% 7N methanolic ammonia in CH2Cl2 provided the title compound (123 mg, 33%) as a brown gum; m/z: ES+ MH+ 461.26.

後処理

  1. temperaturewas heated
  2. temperatureat reflux for 4 h
  3. customovernight
  4. customPart-purification by ion exchange chromatography
  5. washeluting with 7M methanolic ammonia
  6. customprovided crude material that
  7. concentrationwas concentrated in vacuo onto silica
  8. customPurification by FCC
  9. washeluting with 0-5% 7N methanolic ammonia in CH2Cl2 provided impure product as a brown gum
  10. customFurther purification by FCC
  11. washeluting with 0-2% 7N methanolic ammonia in CH2Cl2

出典と根拠

ORDレコード
ord-b4472d6853f84a2fbb6f7d8619157926
出典データセット
uspto-grants-2015_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08946235B2

反応ノート

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