1-Tert-butyl-4-isocyanatobenzene → N-{5-[(3-{[(4-tert-butylphenyl)carbamoyl]amino-}-4-fluorophenyl)(methyl)amino][1,3]thiazolo[5,4-b]pyridin-2-yl}cyclopropanecarboxamide

HRID 2366755Notes

Reaction equation

HRID 2366755 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([N:9]([CH3:25])[C:10]2[N:15]=[C:14]3[S:16][C:17]([NH:19][C:20]([CH:22]4[CH2:24][CH2:23]4)=[O:21])=[N:18][C:13]3=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].[C:26]([C:30]1[CH:35]=[CH:34][C:33]([N:36]=[C:37]=[O:38])=[CH:32][CH:31]=1)([CH3:29])([CH3:28])[CH3:27]>CN(C)C=O.C(OCC)(=O)C>[C:26]([C:30]1[CH:35]=[CH:34][C:33]([NH:36][C:37]([NH:1][C:2]2[CH:3]=[C:4]([N:9]([CH3:25])[C:10]3[N:15]=[C:14]4[S:16][C:17]([NH:19][C:20]([CH:22]5[CH2:23][CH2:24]5)=[O:21])=[N:18][C:13]4=[CH:12][CH:11]=3)[CH:5]=[CH:6][C:7]=2[F:8])=[O:38])=[CH:32][CH:31]=1)([CH3:29])([CH3:27])[CH3:28]

Participants

5

Reactant 2

HCID 27356951-Tert-butyl-4-isocyanatobenzeneHCID 86646059N-{5-[(3-amino-4-fluorophenyl)(methyl)amino][1,3]thiazolo[5,4-b]pyridin-2-yl}cyclopropanecarboxamide

Product 1

HCID 58451261N-{5-[(3-{[(4-tert-butylphenyl)carbamoyl]amino-}-4-fluorophenyl)(methyl)amino][1,3]thiazolo[5,4-b]pyridin-2-yl}cyclopropanecarboxamideYield 17.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-{5-[(3-Amino-4-fluorophenyl)(methyl)amino][1,3]thiazolo[5,4-b]pyridin-2-yl}cyclopropanecarboxamide (120 mg, 0.34 mmol) produced in Example 1(x) was dissolved in N,N-dimethylformamide (1.5 mL), 1-tert-butyl-4-isocyanatobenzene (72 μL, 0.40 mmol) was added, and the mixture was stirred at room temperature for 6 hr. The reaction mixture was diluted with ethyl acetate (10 mL), and washed successively with saturated aqueous sodium hydrogen carbonate solution (10 mL) and saturated brine (10 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=50/50→100/0), and the obtained solution was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to give the title compound (31 mg, 17%) as a colorless powder.

Workup

  1. washwashed successively with saturated aqueous sodium hydrogen carbonate solution (10 mL) and saturated brine (10 mL)
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=50/50→100/0)
  5. concentrationthe obtained solution was concentrated under reduced pressure
  6. customThe residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-4da5f89bf5c44f619ffa4f33c0b3b3dd
Source dataset
uspto-grants-2014_04
Patent number
US08697874B2

Reaction notes

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