2-Aminothiazole → HCID 59212685, compound

HRID 222979Notes

Reaction equation

HRID 222979 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 vaccum 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, 3H), 2.37 (s, 3H), 6.65 (d, J=6.0 Hz, 1H), 6.95 (d, J=3.6 Hz, 1H), 7.15 (t, J=8.4 Hz, 2H), 7.20 (d, J=3.6 Hz, 1H), 7.46 (d, J=9.6 Hz, 1H), 7.54 (m, 2H), 7.96 (d, J=1.6 Hz, 1H), 8.11 (dd, J1=8.0 Hz, J2=1.6 Hz, 1H).

Workup

  1. concentrationconcentrated under vaccum
  2. customto remove DMF

Sources & evidence

ORD record
ord-2c681f6455954aabbd0f3c4ea06a6358
Source dataset
uspto-grants-2012_06
Patent number
US08207176B2

Reaction notes

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