2-Aminothiazole → HCID 59212685, compound

HRID 1806562Notes

Reaction equation

HRID 1806562 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:14]2[N:15]=[C:16]([S:29][CH3:30])[N:17]=[C:18]([C:19]3[CH:20]=[C:21]([CH:25]=[CH:26][C:27]=3[CH3:28])[C:22]([OH:24])=O)[C:13]=2[CH:12]=[CH:11][C:10]1=[O:31].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:65][C:66]1[S:67][CH:68]=[CH:69][N:70]=1>CN(C=O)C.O>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[N:9]1[C:14]2[N:15]=[C:16]([S:29][CH3:30])[N:17]=[C:18]([C:19]3[CH:20]=[C:21]([CH:25]=[CH:26][C:27]=3[CH3:28])[C:22]([NH:65][C:66]3[S:67][CH:68]=[CH:69][N:70]=3)=[O:24])[C:13]=2[CH:12]=[CH:11][C:10]1=[O:31]

Participants

7

Reactant 4

HCID 21552-AminothiazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 575305303-[8-(2,6-Difluorophenyl)-2-(methylthio)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl]-4-methylbenzoic acid

Product 1

HCID 59212685HCID 59212685, compoundYield 81.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 3-[8-(2,6-difluorophenyl)-2-(methylthio)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl]-4-methylbenzoic acid (440 mg, 1.00 mmol) in DMF (15 mL) was mixed with DIEA (0.697 mL, 4.0 mmol), HATU (418 mg, 1.1 mmol) and 2-aminothiazole (150 mg, 1.5 mmol). The reaction mixture was stirred over night, diluted with H2O (0.5 mL), and concentrated under vacuum to remove DMF. Flash chromatography (load column with DCM, mobile phase EtOAc/Hexane) then provided the title compound as a white solid 425 mg (81%). MS (ES) m/z 522 (M+H)+; 1H-NMR (MeOD) δ 2.25 (s, 3 H), 2.37 (s, 3 H), 6.65 (d, J=6.0 Hz, 1 H), 6.95 (d, J=3.6 Hz, 1 H), 7.15 (t, J=8.4 Hz, 2 H), 7.20 (d, J=3.6 Hz, 1 H), 7.46 (d, J=9.6 Hz, 1 H), 7.54 (m, 2 H), 7.96 (d, J=1.6 Hz, 1 H), 8.11 (dd, J=8.0 Hz, J2=1.6 Hz, 1 H).

Workup

  1. concentrationconcentrated under vacuum
  2. customto remove DMF

Sources & evidence

ORD record
ord-ac02873a52fc47409637bfc0312ceee7
Source dataset
uspto-grants-2013_01
Patent number
US08354416B2

Reaction notes

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