2-Aminothiazole → 2,2-dimethyl-3-phenyl-3-(3-phenyl-1H-indazol-6-yl)-N-(thiazol-2-yl)propanamide

HRID 563395Notes

Reaction equation

HRID 563395 reaction equation
[CH3:1][C:2]([CH3:28])([CH:6]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:7]1[CH:15]=[C:14]2[C:10]([C:11]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[N:12][NH:13]2)=[CH:9][CH:8]=1)[C:3]([OH:5])=O.[NH2:29][C:30]1[S:31][CH:32]=[CH:33][N:34]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:1][C:2]([CH3:28])([CH:6]([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[C:7]1[CH:15]=[C:14]2[C:10]([C:11]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[N:12][NH:13]2)=[CH:9][CH:8]=1)[C:3]([NH:29][C:30]1[S:31][CH:32]=[CH:33][N:34]=1)=[O:5]

Participants

6

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 670056622,2-dimethyl-3-phenyl-3-(3-phenyl-1H-indazol-6-yl)propanoic acid

Product 1

HCID 592527712,2-dimethyl-3-phenyl-3-(3-phenyl-1H-indazol-6-yl)-N-(thiazol-2-yl)propanamideYield 28.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 2,2-dimethyl-3-phenyl-3-(3-phenyl-1H-indazol-6-yl)propanoic acid (26 mg, 0.07 mmol), 2-aminothiazole (28 mg, 0.28 mmol), and diisopropylethylamine (0.05 mL) in anhydrous DMF (0.2 mL) was added HATU (106 mg, 0.28 mmol) under argon. After stirring at rt for 2.5 hr and 80° C. for 1 hr, the mixture was concentrated. Purification using reverse phase HPLC (YMC S5 20×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA) gave 2,2-dimethyl-3-phenyl-3-(3-phenyl-1H-indazol-6-yl)-N-(thiazol-2-yl)propanamide (Example 112, 9 mg, 0.02 mmol, 28% yield) as a solid. MS found: (M+H)+=453. 1H-NMR (500 MHz, CDCl3) δ ppm 7.96 (1H, d, J=8.25 Hz) 7.86 (2H, d, J=8.25 Hz) 7.50 (1H, d, J=8.25 Hz) 7.46 (2H, d, J=8.25 Hz) 7.39-7.43 (2H, m) 7.35 (2H, d, J=7.70 Hz) 7.17-7.26 (4 H, m), 6.96 (1H, d, J=3.30 Hz) 4.62 (1H, s) 1.45 (6H, d, J=3.85 Hz).

Workup

  1. concentrationthe mixture was concentrated
  2. customPurification
  3. customphase HPLC (YMC S5 20×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA)

Sources & evidence

ORD record
ord-f159853ab02b41e2b8f7a9eface7f24b
Source dataset
uspto-grants-2011_11
Patent number
US08067447B2

Reaction notes

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