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

HRID 563410
Notes
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Reaction equation

HRID 563410 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]([CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[C:18]([CH3:23])([CH3:22])[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.[NH2:64][C:65]1[S:66][CH:67]=[CH:68][N:69]=1>CN(C=O)C>[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]([CH2:24][C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)[C:18]([CH3:22])([CH3:23])[C:19]([NH:64][C:65]4[S:66][CH:67]=[CH:68][N:69]=4)=[O:21])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

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 670060253-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-4-phenylbutanoic acid

Product 1

HCID 59252810
3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-4-phenyl-N-(thiazol-2-yl)butanamide
Yield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-4-phenylbutanoic acid (10 mg, 0.025 mmol) and diisopropylethylamine (0.05 mL) in anhydrous DMF (0.2 mL) was added HATU (25 mg, 0.066 mmol) at rt under argon. After stirring at rt for 10 min, 2-aminothiazole (15 mg, 0.15 mmol) was added. The reaction mixture was stirred at rt for 2.5 hr, 40° C. for 1 hr, and 80° 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)-2,2-dimethyl-4-phenyl-N-(thiazol-2-yl)butanamide (Example 138, 7 mg, 0.01 mmol, 40% yield) as a white solid. MS found: (M+H)+=485. 1H-NMR (400 MHz, CDCl3) δ ppm 8.00 (1H, s) 7.53-7.58 (3H, m) 7.44 (1H, d, J=8.65 Hz) 7.35 (1H, d, J=3.56 Hz) 7.23 (1H, d, J=7.63 Hz) 7.11-7.15 (2H, m) 6.89-6.99 (7H, m) 3.63 (1H, dd, J=10.43, 4.32 Hz) 2.97-3.08 (2H, m) 1.37 (3H, s) 1.18 (3H, s).

Workup

  1. stirringThe reaction mixture was stirred at rt for 2.5 hr, 40° C. for 1 hr
  2. wait80° C. for 30 min
  3. customPurification
  4. 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-84836105409c440dbe03edb551b3d359
Source dataset
uspto-grants-2011_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08067447B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes