Diisopropylethylamine → N-(3-Amino-2,2-difluoro-propyl)-4-fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzamide

HRID 1985769

Reaction equation

HRID 1985769 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[NH:11][CH2:12][C:13]1[S:17][C:16]([NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)=[N:15][CH:14]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:49][C:50]([F:55])([CH2:53][NH2:54])[CH2:51][NH2:52].CCN(C(C)C)C(C)C>CN(C=O)C.C1COCC1.C(Cl)Cl>[NH2:52][CH2:51][C:50]([F:55])([F:49])[CH2:53][NH:54][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][C:2]([F:1])=[C:3]([NH:11][CH2:12][C:13]2[S:17][C:16]([NH:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=3)=[N:15][CH:14]=2)[CH:4]=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 199026522,2-Difluoropropane-1,3-diamineHCID 220190564-Fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzoic acid2×

Product 1

HCID 22019140N-(3-Amino-2,2-difluoro-propyl)-4-fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzamideYield 65%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 4-fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzoic acid (compound 52A, 21 mg, 0.06 mmol) and HATU (38 mg, 0.1 mmol) in DMF (0.2 ml) and THF (0.4 ml), were added 2,2-difluoro-1,3-propanediamine (ref. Tetrahedron, 8617, 1994) (60 mg, 0.54 mmol) and DIPEA (26 mg, 0.2 mmol). The resulting mixture was stirred at RT for 18 h, then diluted with CH2Cl2, washed with brine, dried over Na2SO4 and concentrated. The residue was purified by flash column chromatography [silica gel, 5% (NH3/MeOH(2M) in EtOAc] to afford the title compound (17 mg, 65%) as a white solid. LC/MS; (M+H)+=437.

Workup

  1. washwashed with brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customThe residue was purified by flash column chromatography [silica gel, 5% (NH3/MeOH(2M) in EtOAc]

Sources & evidence

ORD record
ord-7913a66cfb9b4b26b68b10f5cc238c4e
Source dataset
uspto-grants-2009_06
Patent number
US07547711B2

Linked notes

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