Diisopropylethylamine → N-[4-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-3-fluorophenyl]-1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide

HRID 2095900Notes

Reaction equation

HRID 2095900 reaction equation
[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[N:12]=[C:11]3[S:13][C:14]([NH:16][C:17]([CH:19]4[CH2:21][CH2:20]4)=[O:18])=[N:15][C:10]3=[CH:9][CH:8]=2)=[C:4]([F:24])[CH:3]=1.[F:25][C:26]1[CH:31]=[CH:30][C:29]([N:32]2[C:37]([CH3:38])=[CH:36][CH:35]=[C:34]([C:39](O)=[O:40])[C:33]2=[O:42])=[CH:28][CH:27]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C.C(OCC)(=O)C.O1CCCC1>[CH:19]1([C:17]([NH:16][C:14]2[S:13][C:11]3[C:10]([N:15]=2)=[CH:9][CH:8]=[C:7]([O:6][C:5]2[CH:22]=[CH:23][C:2]([NH:1][C:39]([C:34]4[C:33](=[O:42])[N:32]([C:29]5[CH:28]=[CH:27][C:26]([F:25])=[CH:31][CH:30]=5)[C:37]([CH3:38])=[CH:36][CH:35]=4)=[O:40])=[CH:3][C:4]=2[F:24])[N:12]=3)=[O:18])[CH2:21][CH2:20]1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210815291-(4-Fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acidHCID 58158529N-[5-(4-amino-2-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 58158619N-[4-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-3-fluorophenyl]-1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamideYield 88%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-[5-(4-Amino-2-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide (240 mg, 0.70 mmol), 1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid (190 mg, 0.77 mmol) and HATU (340 mg, 0.91 mmol) were suspended in N,N′-dimethylformamide (3.0 mL), and N,N-diisopropylethylamine (0.24 mL, 1.4 mmol) was added. After stirring at room temperature for 8 hr, the mixture was diluted with ethyl acetate (5.0 mL) and tetrahydrofuran (5.0 mL). The mixture was washed twice with saturated aqueous sodium hydrogen carbonate solution, and the organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and ethyl acetate was added to the residue. The resulting precipitate was collected by filtration to give the title compound (350 mg, 0.61 mmol, 88%) as a pale-yellow solid.

Workup

  1. washThe mixture was washed twice with saturated aqueous sodium hydrogen carbonate solution
  2. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  3. customThe solvent was evaporated under reduced pressure, and ethyl acetate
  4. additionwas added to the residue
  5. filtrationThe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-9d4fc6ce4ab146a1b3f3bd54a35f0fdd
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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