Methanol → N-[5-(3-amino-4-chlorophenoxy) [1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide

HRID 2366781Notes

Reaction equation

HRID 2366781 reaction equation
[BH4-].[Na+].CO.[Cl:5][C:6]1[CH:27]=[CH:26][C:9]([O:10][C:11]2[N:16]=[C:15]3[S:17][C:18]([NH:20][C:21]([CH:23]4[CH2:25][CH2:24]4)=[O:22])=[N:19][C:14]3=[CH:13][CH:12]=2)=[CH:8][C:7]=1[NH:28]C(=O)C(F)(F)F>C(O)C.C(OCC)(=O)C>[NH2:28][C:7]1[CH:8]=[C:9]([CH:26]=[CH:27][C:6]=1[Cl:5])[O:10][C:11]1[N:16]=[C:15]2[S:17][C:18]([NH:20][C:21]([CH:23]3[CH2:25][CH2:24]3)=[O:22])=[N:19][C:14]2=[CH:13][CH:12]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 57387328N-(5-{4-chloro-3-[(trifluoroacetyl)amino]phenoxy}[1,3]thiazolo[5,4-b]pyridin-2-yl)cyclopropanecarboxamide

Product 1

HCID 57384284N-[5-(3-amino-4-chlorophenoxy) [1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamideYield 75%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

Sodium borohydride (5.63 g, 149 mmol) was suspended in ethanol (100 mL), and methanol (66 mL) was gradually added. While cooling in a water bath, to the obtained reaction mixture was added N-(5-{4-chloro-3-[(trifluoroacetyl)amino]phenoxy}[1,3]thiazolo[5,4-b]pyridin-2-yl)cyclopropanecarboxamide (3.4 g, 7.44 mmol) powder by small portions, and thereafter the mixture was stirred at room temperature, for 1 hr. The reaction mixture was diluted with ethyl acetate (150 mL), and partitioned with water (200 ml). The organic layer was concentrated under reduced pressure. The residue was diluted with ethyl acetate (200 mL), and washed with saturated brine (100 mL). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=100/0), and triturated with diisopropyl ether to give the title compound (2.00 g, 75%) as a colorless powder.

Workup

  1. temperatureWhile cooling in a water bath, to the obtained reaction mixture
  2. custompartitioned with water (200 ml)
  3. concentrationThe organic layer was concentrated under reduced pressure
  4. additionThe residue was diluted with ethyl acetate (200 mL)
  5. washwashed with saturated brine (100 mL)
  6. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=100/0)
  9. customtriturated with diisopropyl ether

Sources & evidence

ORD record
ord-35398e8ded0d4476b2735b21cb899481
Source dataset
uspto-grants-2014_04
Patent number
US08697874B2

Reaction notes

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