2-Aminothiazole → 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-3-methyl-N-(thiazol-2-yl)butanamide

HRID 563400Notes

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]([C:17]([CH3:23])([CH3:22])[CH2:18][C:19]([OH:21])=O)=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=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.[NH2:57][C:58]1[S:59][CH:60]=[CH:61][N:62]=1>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]([C:17]([CH3:23])([CH3:22])[CH2:18][C:19]([NH:57][C:58]4[S:59][CH:60]=[CH:61][N:62]=4)=[O:21])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a stirred solution of 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-3-methylbutanoic acid (14 mg, 0.045 mmol) and diisopropylethylamine (0.05 mL) in anhydrous DMF (0.3 mL) was added HATU (30 mg, 0.079 mmol) at 0° C. under argon. After stirring at 0° C. for 5 min, 2-aminothiazole (15 mg, 0.15 mmol) was added. The reaction mixture was stirred at rt for 5 min and 50° C. for 30 min. 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-indazol-5-yl)-3-methyl-N-(thiazol-2-yl)butanamide (Example 114, 9 mg, 0.02 mmol, 44% yield) as a white solid. MS found: (M+H)+=395. 1H-NMR (400 MHz, CDCl3) δ ppm 8.04 (1H, s) 7.67 (1H, s) 7.58 (2H, dd, J=8.90, 4.83 Hz) 7.53 (1H, d, J=9.16 Hz) 7.40-7.46 (1H, m) 7.25 (1H, s) 7.14 (2H, t, J=8.65 Hz) 6.87 (1H, s) 2.81 (2H, s) 1.51 (6H, s).

Workup

stirringThe reaction mixture was stirred at rt for 5 min and 50° C. for 30 min
customPurification
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-25a2254814cb401fb95e89998fb9270b
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08067447B2

Reaction notes

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