Trifluoroacetic acid → 1-amino-N-{6-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinyl}cyclobutanecarboxamide

HRID 527556Notes

Reaction equation

HRID 527556 reaction equation
[CH3:1][C:2]1([CH3:33])[C:6]2[C:7]([O:11][C:12]3[N:17]=[CH:16][C:15]([NH:18][C:19]([C:21]4([NH:25]C(=O)OC(C)(C)C)[CH2:24][CH2:23][CH2:22]4)=[O:20])=[CH:14][CH:13]=3)=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3]1.C(O)(C(F)(F)F)=O>ClCCl>[NH2:25][C:21]1([C:19]([NH:18][C:15]2[CH:16]=[N:17][C:12]([O:11][C:7]3[C:6]4[C:2]([CH3:33])([CH3:1])[CH2:3][O:4][C:5]=4[CH:10]=[CH:9][CH:8]=3)=[CH:13][CH:14]=2)=[O:20])[CH2:24][CH2:23][CH2:22]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 866984251,1-Dimethylethyl {1-[({6-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinyl}amino)carbonyl]cyclobutyl}carbamate2×

Product 1

HCID 679668331-amino-N-{6-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinyl}cyclobutanecarboxamideYield 98.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1,1-dimethylethyl {1-[({6-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinyl}amino)carbonyl]cyclobutyl}carbamate (Intermediate 69, 23.5 mg) in dry dichloromethane (3.5 ml), TFA (159 μl, 2.07 mmol) was slowly added at 0° C. and the reaction mixture was stirred for 2 hours at room temperature. The solvent and the excess of TFA were evaporated and the residue was purified with an SCX cartridge. The cartridge was washed with 3 CV of methanol, then the compound was adsorbed on the cartridge, washed with 5 CV of methanol and desorbed with 2 CV of methanolic ammonia (1N). This afforded the title compound (18 mg).

Workup

  1. customThe solvent and the excess of TFA were evaporated
  2. customthe residue was purified with an SCX cartridge
  3. washThe cartridge was washed with 3 CV of methanol
  4. washwashed with 5 CV of methanol

Sources & evidence

ORD record
ord-bbd71462a9944b6e8ff517bb539987fc
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

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