2-Aminothiazole → HCID 59252882, compound

HRID 563390Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[C:18]([CH3:23])([CH3:22])[C:19]([OH:21])=O)=[CH:14][CH:15]=3)[CH:10]=[CH:9]2)=[CH:4][CH:3]=1.[NH2:30][C:31]1[S:32][CH:33]=[CH:34][N:35]=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>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)[C:18]([CH3:22])([CH3:23])[C:19]([NH:30][C:31]4[S:32][CH:33]=[CH:34][N:35]=4)=[O:21])=[CH:14][CH:15]=3)[CH:10]=[CH:9]2)=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a stirred solution of 3-(1-(4-fluorophenyl)-1H-indol-5-yl)-2,2-dimethyl-3-phenylpropanoic acid (23 mg, 0.059 mmol), 2-aminothiazole (18 mg, 0.18 mmol), and diisopropylethylamine (0.03 mL, 0.18 mmol) in anhydrous DMF (0.3 mL) was added HATU (68 mg, 0.18 mmol) under argon. The reaction mixture was stirred at rt for 5 min and at 80° C. for 5 hr. Concentration and 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 3-(1-(4-fluorophenyl)-1H-indol-5-yl)-2,2-dimethyl-3-phenyl-N-(thiazol-2-yl)propanamide (Example 110, 6 mg, 0.013 mmol, 22% yield) as a pink solid. MS found: (M+H)+=470. 1H-NMR (400 MHz, CDCl3) δ ppm 7.67 (1H, s) 7.32-7.43 (5H, m) 7.33 (1H, d, J=8.65 Hz) 7.22-7.28 (3H, m) 7.14-7.20 (4H, m) 6.94 (1H, d, J=3.56 Hz) 6.60 (1H, d, J=3.05 Hz) 4.59 (1H, s) 1.46 (6H, d, J=2.54 Hz).

Workup

concentrationConcentration and purification
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-a77f12dac51f4efc81f6ad28d3de9d0d
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08067447B2

Reaction notes

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