Ammonium Chloride → HCID 89544668、化合物

HRID 2283432ノート

反応式

HRID 2283432 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:11][CH2:12][C:13]([CH3:18])([CH3:17])[C:14](O)=[O:15])[CH2:9][CH3:10])=[C:4]([F:19])[C:3]=1[C:20]([C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1)=[O:21].[Cl-].[NH4+].CC[N:32](C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:11][CH2:12][C:13]([CH3:17])([CH3:18])[C:14]([NH2:32])=[O:15])[CH2:9][CH3:10])=[C:4]([F:19])[C:3]=1[C:20]([C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1)=[O:21]

参加物

6

反応物 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89544960HCID 89544960、化合物

生成物 1

HCID 89544668HCID 89544668、化合物収率 5.2%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

Step 5 To a solution of crude 3-{(R)-1-[4-Chloro-2-fluoro-3-(pyridine-3-carbonyl)-phenyl]-propylamino}-2,2-dimethyl-propionic acid (1.15 mmol) in DMF (7 mL) was added ammonium chloride (315 mg, 5.8 mmol, 5 eq), DIPEA (1.41 mL, 8.1 mmol, 7 eq.) and then HATU (661 mg, 1.74 mmol, 1.5 eq.) and the reaction stirred for 18 h. The mixture was partitioned between EtOAc (20 mL) and water (20 mL). The aqueous was extracted with further EtOAc (20 mL) and then the combined organic phase washed with water (3×20 mL) and brine (20 mL) before it was dried (MgSO4), filtered and concentrated. Purified by prepHPLC, basic conditions, and then concentrated. Dissolved in DCM and 1.1 eq. 2 M HCl in Et2O was added. Concentrated and dried in a vacuum oven to give 3-{(R)-1-[4-Chloro-2-fluoro-3-(pyridine-3-carbonyl)-phenyl]-propylamino}-2,2-dimethyl-propionamide (26 mg, 0.06 mmol).

後処理

  1. customThe mixture was partitioned between EtOAc (20 mL) and water (20 mL)
  2. extractionThe aqueous was extracted with further EtOAc (20 mL)
  3. washthe combined organic phase washed with water (3×20 mL) and brine (20 mL) before it
  4. dry with materialwas dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurified by prepHPLC, basic conditions
  8. concentrationconcentrated
  9. dissolutionDissolved in DCM
  10. addition2 M HCl in Et2O was added
  11. concentrationConcentrated
  12. customdried in a vacuum oven

出典と根拠

ORDレコード
ord-f3fa67835beb49858f5e038fa3568ea7
出典データセット
uspto-grants-2015_09
特許番号
US09145354B2

反応ノート

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