Diisopropylethylamine → Tert-butyl 4-(4-(5-amino-2-(2,6-difluorophenyl)thiazole-4-carboxamido)isothiazol-5-yloxy)piperidine-1-carboxylate

HRID 871038Notes

Reaction equation

HRID 871038 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][S:5][C:6]=1[O:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1.[NH2:21][C:22]1[S:26][C:25]([C:27]2[C:32]([F:33])=[CH:31][CH:30]=[CH:29][C:28]=2[F:34])=[N:24][C:23]=1[C:35](O)=[O:36].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[NH2:21][C:22]1[S:26][C:25]([C:27]2[C:32]([F:33])=[CH:31][CH:30]=[CH:29][C:28]=2[F:34])=[N:24][C:23]=1[C:35]([NH:1][C:2]1[CH:3]=[N:4][S:5][C:6]=1[O:7][CH:8]1[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:12][CH2:13]1)=[O:36]

Participants

7

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 594556885-Amino-2-(2,6-difluorophenyl)thiazole-4-carboxylic acidHCID 86720857Tert-butyl 4-(4-aminoisothiazol-5-yloxy)piperidine-1-carboxylate

Product 1

HCID 86720858Tert-butyl 4-(4-(5-amino-2-(2,6-difluorophenyl)thiazole-4-carboxamido)isothiazol-5-yloxy)piperidine-1-carboxylateYield 19.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

tert-butyl 4-(4-aminoisothiazol-5-yloxy)piperidine-1-carboxylate (1D4) (47 mg, 0.156 mmol), 5-amino-2-(2,6-difluorophenyl)thiazole-4-carboxylic acid (1E) (40 mg, 0.156 mmol), HATU (71 mg, 0.187 mmol) and DIEA (84 μL, 0.468 mmol) were mixed in DMF (5 mL), stirred at 50° C. for 1 hour, cooled to room temperature, diluted with ethyl acetate (50 mL), washed with brine, dried over Na2SO4, and concentrated in vacuo at room temperature (25° C.). The residue was purified with flash column (eluent: 10-30% ethyl acetate/petroleum ether) to afford the product tert-butyl 4-(4-(5-amino-2-(2,6-difluorophenyl)thiazole-4-carboxamido)isothiazol-5-yloxy)piperidine-1-carboxylate (1A) (17 mg, 0.031 mmol).

Workup

  1. temperaturecooled to room temperature
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo at room temperature (25° C.)
  5. customThe residue was purified with flash column (eluent: 10-30% ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-05bbda1e972b40e08fdacb8361c3d88d
Source dataset
uspto-grants-2015_03
Patent number
US08969584B2

Reaction notes

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