Trifluoroacetic acid → 2-Amino-1-[4-cyclopentyl-6-(6-fluoro-1H-indol-3-yl)-hexahydro-pyrrolo[3,2-b]pyrrol-1-yl]-3,3-dimethyl-butan-1-one

HRID 1949626Notes

Reaction equation

HRID 1949626 reaction equation
C(OC(=O)[NH:7][CH:8]([C:13]([N:15]1[CH2:19][CH2:18][CH:17]2[N:20]([CH:33]3[CH2:37][CH2:36][CH2:35][CH2:34]3)[CH2:21][CH:22]([C:23]3[C:31]4[C:26](=[CH:27][C:28]([F:32])=[CH:29][CH:30]=4)[NH:25][CH:24]=3)[CH:16]12)=[O:14])[C:9]([CH3:12])([CH3:11])[CH3:10])(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:7][CH:8]([C:9]([CH3:12])([CH3:11])[CH3:10])[C:13]([N:15]1[CH2:19][CH2:18][CH:17]2[N:20]([CH:33]3[CH2:34][CH2:35][CH2:36][CH2:37]3)[CH2:21][CH:22]([C:23]3[C:31]4[C:26](=[CH:27][C:28]([F:32])=[CH:29][CH:30]=4)[NH:25][CH:24]=3)[CH:16]12)=[O:14]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67408721{1-[4-Cyclopentyl-6-(6-fluoro-1H-indol-3-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propyl}-carbamic acid tert-butyl ester

Product 1

HCID 674083852-Amino-1-[4-cyclopentyl-6-(6-fluoro-1H-indol-3-yl)-hexahydro-pyrrolo[3,2-b]pyrrol-1-yl]-3,3-dimethyl-butan-1-oneYield 96.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution containing 38 (0.28 g, 0.53 mmol) in DCM (10 mL) was added TFA (3 mL) at ambient temperature. After 90 min, the reaction mixture was concentrated in vacuo. The residue was dissolved in EtOAc and the organic solution was washed successively with saturated aqueous NaHCO3 and brine, dried over anhydrous Na2SO4, filtered, and concentrated to afford 218 mg of 39 which was used without further purification. 1H NMR (CDCl3, 300 MHz), mixture of rotamers: δ9.31 (s, 0.5H), 8.24 (s, 0.5H), 7.86 (dd, J=5.4, 8.7 Hz, 0.5H), 7.54 (dd, J=5.4, 8.7 Hz, 0.5H), 7.28 (s, 1H), 7.00 (dd, J=2.4, 9.9 Hz, 0.5H), 6.96-9.6.91 (m, 1H), 6.86-6.79 (m, 0.5H), 4.98 (app t, J=8.1 Hz, 0.5H), 4.80 (app t, J=7.8 Hz, 0.5H), 4.16-4.09 (m, 0.5H), 3.94-3.81 (m, 1.5H), 3.54-3.45 (m, 1H), 3.29-3.06 (m, 2H), 2.90-2.70 (m, 2H), 2.26-2.21 (m, 0.5H), 2.12-2.05 (m, 0.5H), 1.90-1.68 (m, 4H), 1.60-1.50 (m, 4H), 1.16 (br s, 2H), 0.80 (s, 4.5H), 0.21 (s, 4.5H) ppm. Mass spectrum, m/z [427.3] (M+H)+.

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolved in EtOAc
  3. washthe organic solution was washed successively with saturated aqueous NaHCO3 and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-01f7a00d886f4e239d4f6a73b2e8f4cd
Source dataset
uspto-grants-2013_03
Patent number
US08399683B2

Reaction notes

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