2-Aminothiazole → HCID 59252846, compound

HRID 563386Notes

Reaction equation

HRID 563386 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([CH:10]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:11]([CH3:16])([CH3:15])[C:12]([OH:14])=O)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[NH2:23][C:24]1[S:25][CH:26]=[CH:27][N:28]=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>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([CH:10]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:11]([CH3:15])([CH3:16])[C:12]([NH:23][C:24]3[S:25][CH:26]=[CH:27][N:28]=3)=[O:14])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

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 59252803HCID 59252803, compound

Product 1

HCID 59252846HCID 59252846, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 3-(1H-indol-5-yl)-2,2-dimethyl-3-phenylpropanoic acid (0.31 g, 1.1 mmol), 2-aminothiazole (0.2 g, 2 mmol), and diisopropylethylamine (0.5 mL) in anhydrous DMF (3 mL) was added HATU (1 g, 2.7 mmol) under argon. After the reaction mixture was stirred at rt for 14 hr and 80° C. for 6 hr, it was concentrated, dissolved in ethyl acetate (20 mL), washed with saturated aqueous sodium bicarbonate solution (10 mL), brine (10 mL), dried (Na2SO4), and concentrated. Silica gel flash chromatography gave 3-(1H-indol-5-yl)-2,2-dimethyl-3-phenyl-N-(thiazol-2-yl)propanamide (Example 107, 0.3 g, 0.8 mmol, 75% yield) as a yellow solid. MS found: (M+H)+=376. 1H-NMR (400 MHz, MeOD) δ ppm 7.60 (1H, s) 7.43 (2H, d, J=7.12 Hz) 7.38 (1H, d, J=3.56 Hz) 7.20-7.29 (3H, m) 7.12-7.20 (2H, m) 7.10 (1H, d) 7.04 (1H, d, J=3.56 Hz) 6.38 (1H, d, J=3.05 Hz) 4.70 (1H, s) 4.62 (1H, s) 1.43 (6H, d, J=4.07 Hz).

Workup

  1. concentrationit was concentrated
  2. dissolutiondissolved in ethyl acetate (20 mL)
  3. washwashed with saturated aqueous sodium bicarbonate solution (10 mL), brine (10 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-16a12c9ba3b54df3b01a0cc5b4e817f9
Source dataset
uspto-grants-2011_11
Patent number
US08067447B2

Reaction notes

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