Trifluoroacetic acid → HCID 51354224, compound

HRID 1879395Notes

Reaction equation

HRID 1879395 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@@H:9]1[CH2:19][CH2:18][C@H:17]([CH2:20][C:21](=[O:38])[N:22]2[CH2:27][CH2:26][CH:25]([N:28]3[C:36]4[C:31](=[N:32][CH:33]=[CH:34][CH:35]=4)[NH:30][C:29]3=[O:37])[CH2:24][CH2:23]2)[C:12]2=[N:13][CH:14]=[CH:15][CH:16]=[C:11]2[C@H:10]1[NH:39]C(=O)OC(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:39][C@@H:10]1[C:11]2[C:12](=[N:13][CH:14]=[CH:15][CH:16]=2)[C@@H:17]([CH2:20][C:21]([N:22]2[CH2:23][CH2:24][CH:25]([N:28]3[C:36]4[C:31](=[N:32][CH:33]=[CH:34][CH:35]=4)[NH:30][C:29]3=[O:37])[CH2:26][CH2:27]2)=[O:38])[CH2:18][CH2:19][C@H:9]1[C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=1[F:1]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 51354223HCID 51354223, compound

Product 1

HCID 51354224HCID 51354224, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a methylene chloride (5 mL) solution of tert-butyl (5S,6S,9R)-6-(2,3-difluorophenyl)-9-(2-oxo-2-(4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidin-1-yl)ethyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-5-ylcarbamate (0.1452 g, 0.229 mmol) was added TFA (1 ml, 12.98 mmol) at room temperature. The reaction was stirred at room temperature for 3 h before removal of the solvent in vacuo. The crude mixture was partitioned between ethyl acetate and water. Sodium bicarbonate (sat) was added and the ethyl acetate layer was separated. The ethyl acetate layer was dried (sodium sulfate), filtered and concentrated. Flash chromatography using methanol in methylene chloride from 0 to 10% gave a product that was still somewhat impure. The product was further purified by prep TLC eluting with 10% methanol in methylene chloride (25.9 mg, 20%): MS(ESI)[M+H+]=533.29; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.47 (1H, td, J=5.3, 3.5 Hz), 8.09 (1H, d, J=5.3 Hz), 7.49-7.58 (1H, m), 7.27-7.34 (1H, m), 7.18 (1H, ddd, J=15.3, 7.4, 4.9 Hz), 6.95-7.10 (4H, m), 4.87 (1H, d, J=13.1 Hz), 4.57-4.76 (1H, m), 4.44 (1H, d, J=13.1 Hz), 4.10-4.33 (2H, m), 3.46-3.67 (1H, m), 3.20-3.40 (2H, m), 2.39-2.79 (3H, m), 1.50-2.33 (9H, m).

Workup

  1. customThe crude mixture was partitioned between ethyl acetate and water
  2. additionSodium bicarbonate (sat) was added
  3. customthe ethyl acetate layer was separated
  4. dry with materialThe ethyl acetate layer was dried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customgave a product that
  8. customThe product was further purified by prep TLC
  9. washeluting with 10% methanol in methylene chloride (25.9 mg, 20%)

Sources & evidence

ORD record
ord-87ac1509b27f490f883d660431b254ac
Source dataset
uspto-grants-2012_11
Patent number
US08314117B2

Reaction notes

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