3-Hydroxybutanal → [2-Chloro-4-(2,4-difluoro-phenylamino)-phenyl]-[5-(3-hydroxy-butylamino)-2-methyl-phenyl]-methanone

HRID 1012634Notes

Reaction equation

HRID 1012634 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:26])=[C:6]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=3[F:24])=[CH:12][C:11]=2[Cl:25])=[O:9])[CH:7]=1.[OH:27][CH:28]([CH3:32])[CH2:29][CH:30]=O>CO>[Cl:25][C:11]1[CH:12]=[C:13]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=2[F:24])[CH:14]=[CH:15][C:10]=1[C:8]([C:6]1[CH:7]=[C:2]([NH:1][CH2:30][CH2:29][CH:28]([OH:27])[CH3:32])[CH:3]=[CH:4][C:5]=1[CH3:26])=[O:9]

Participants

4

Reactant 2

HCID 78973-Hydroxybutanal2×HCID 11538012(5-Amino-2-methyl-phenyl)-[2-chloro-4-(2,4-difluoro-phenylamino)-phenyl]-methanone

Product 1

HCID 58677686[2-Chloro-4-(2,4-difluoro-phenylamino)-phenyl]-[5-(3-hydroxy-butylamino)-2-methyl-phenyl]-methanone

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Compound 494 (0.033 g, 0.09 mmol) was suspended in MeOH (1 mL). 3-Hydroxy-butyraldehyde (0.023 g, 0.27 mmol) and NaCN(BH3) (0.055 g, 0.88 mmol) were added. The suspension was stirred at room temperature for 18 h. 3-Hydroxy-butyraldehyde (0.023 g, 0.27 mmol) and NaCN(BH3) (0.055 g, 0.88 mmol) were added again and the suspension was stirred at room temperature for 24 h. The reaction mixture was concentrated in vacuo. The residue was dissolved in EtOAc and the organic phase was washed with brine. The water phase was extracted with EtOAc and the combined organic phases were dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by flash chromatography using MeOH/CH2Cl2 1:50 as the eluent. This afforded the title compound as oil. 13C NMR (CDCl3) δ 196.7, 159.0 (dd), 155.4 (dd), 147.3, 146.0, 139.6, 135.0, 133.5, 132.0, 129.9, 126.7, 124.6 (dd), 124.0 (dd), 116.3, 115.9, 114.6, 112.8, 111.6 (dd), 104.9 (dd), 67.5, 42.1, 38.0, 24.0, 19.4

Workup

  1. stirringthe suspension was stirred at room temperature for 24 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionThe residue was dissolved in EtOAc
  4. washthe organic phase was washed with brine
  5. extractionThe water phase was extracted with EtOAc
  6. dry with materialthe combined organic phases were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-594652d817df48b58b0c2ccaf497811b
Source dataset
uspto-grants-2011_07
Patent number
US07977387B2

Reaction notes

Loading…