Trifluoroacetic acid → 3-[4-(1-Amino-cyclobutyl)-phenyl]-2-phenyl-7H-pyrano[2,3-e]indazol-4-one

HRID 1037238Notes

Reaction equation

HRID 1037238 reaction equation
C(OC(=O)[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19](=[O:45])[C:20]4[C:21]([O:37][C:38]=3[C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)=[C:22]3[C:26](=[CH:27][CH:28]=4)[N:25](COCC[Si](C)(C)C)[N:24]=[CH:23]3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl.CO>[NH2:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19](=[O:45])[C:20]4[C:21]([O:37][C:38]=3[C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=3)=[C:22]3[C:26](=[CH:27][CH:28]=4)[NH:25][N:24]=[CH:23]3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67067761(1-{-4-[4-Oxo-2-phenyl-7-(2-trimethylsilanyl-ethoxymethyl)-4,7-dihydro-pyrano[2,3-e]indazol-3-yl]-phenyl}-cyclobutyl)-carbamic acid tert-butyl ester

Product 1

HCID 510295913-[4-(1-Amino-cyclobutyl)-phenyl]-2-phenyl-7H-pyrano[2,3-e]indazol-4-oneYield 47.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (1-{-4-[4-oxo-2-phenyl-7-(2-trimethylsilanyl-ethoxymethyl)-4,7-dihydro-pyrano[2,3-e]indazol-3-yl]-phenyl}-cyclobutyl)-carbamic acid tert-butyl ester (67 mg, 0.13 mmol) in DCM (2.0 mL), was added TFA (500 μL, 6.7 mmol). The reaction mixture was stirred at RT for 1 hour. The solution was diluted with methanol (10 mL) and loaded onto an SCX-2 cartridge. The cartridge was washed repeatedly with methanol before elution with 2 M ammonia in methanol. The eluent was collected and concentrated in vacuo. The resulting residue was subjected to flash chromatography (SiO2, gradient 7-10% methanol in DCM) to give the title compound as a light pink solid (25 mg, 47%). 1H NMR (400 MHz, DMSO-d6): δ 8.54 (d, J=1 Hz, 1H), 8.00 (d, J=9 Hz, 1H), 7.63 (dd, J=1 and 9 Hz, 1H), 7.52-7.49 (m, 2H), 7.44-7.34 (m, 5H), 7.17-7.14 (m, 2H), 2.41-2.33 (m, 2H), 2.11-2.03 (m, 2H), 2.03-1.92 (m, 1H), 1.70-1.60 (m, 1H). LCMS (Method E): RT=3.09 min, [M+H]+=407.

Workup

  1. washThe cartridge was washed repeatedly with methanol before elution with 2 M ammonia in methanol
  2. customThe eluent was collected
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5939d09f053f4fee9a01fb8e68f83d84
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Reaction notes

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