Methanol → HCID 70983774, compound

HRID 403347Notes

Reaction equation

HRID 403347 reaction equation
[O:1]=[C:2]1[NH:10][C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[N:3]1[CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C@H:20]2[C:30]3[C:25](=[N:26][CH:27]=[CH:28][N:29]=3)[C@@H:24]([NH:31]C(OC(C)(C)C)=O)[C@H:23]([C:39]3[CH:44]=[CH:43][CH:42]=[C:41]([F:45])[C:40]=3[F:46])[CH2:22][CH2:21]2)=[O:18])[CH2:13][CH2:12]1.FC(F)(F)C(O)=O.CO>C(Cl)Cl>[O:1]=[C:2]1[NH:10][C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[N:3]1[CH:11]1[CH2:12][CH2:13][N:14]([C:17]([O:19][C@H:20]2[C:30]3[C:25](=[N:26][CH:27]=[CH:28][N:29]=3)[C@@H:24]([NH2:31])[C@H:23]([C:39]3[CH:44]=[CH:43][CH:42]=[C:41]([F:45])[C:40]=3[F:46])[CH2:22][CH2:21]2)=[O:18])[CH2:15][CH2:16]1

Participants

5

Reactant 3

HCID 887MethanolHCID 6422Trifluoroacetic acidHCID 70984361HCID 70984361, compound

Product 1

HCID 70983774HCID 70983774, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

In a 50 mL round-bottomed flask was dissolved (5R,8S,9S)-9-(tert-butoxycarbonylamino)-8-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyrazin-5-yl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate (38.1 mg, 0.060 mmol) in methylene chloride (1 mL) to give a colorless solution. trifluoroacetic acid (0.5 mL) was added, and the mixture was stirred at rt for 1 h. LCMS showed complete conversion. Volatiles were removed in vacuo, and the residue was partitioned between ethyl acetate/0.5N sodium hydroxide/saturated sodium bicarbonate solution. The layers were separated. The organic layer was dried and concentrated to give a tan oil. flash column chromatography up to 10% methanol (2M ammonia) in methylene chloride afforded the desired product (22 mg, 69%) as a white solid: MS (ESI)[M+H+]=536.2; 1H NMR (400 MHz, CDCl3) δ 8.50 (s, 2H), 8.11 (d, J=4.9 Hz, 1H), 7.42 (s, J=16.5 Hz, 1H), 7.17-6.95 (m, 4H), 6.24-5.97 (m, 2H), 4.69-4.34 (m, 4H), 3.31-2.81 (m, 3H), 2.37 (dd, J=23.5, 13.6 Hz, 4H), 2.17-1.67 (m, 6H); 19F NMR (376 MHz, CDCl3) δ −137.10-−137.50 (m), −142.45 (d, J=20.6 Hz).

Workup

  1. customto give a colorless solution
  2. customVolatiles were removed in vacuo
  3. customthe residue was partitioned between ethyl acetate/0.5N sodium hydroxide/saturated sodium bicarbonate solution
  4. customThe layers were separated
  5. customThe organic layer was dried
  6. concentrationconcentrated
  7. customto give a tan oil

Sources & evidence

ORD record
ord-bf06fa1772644bac9033bb93c1d7f18c
Source dataset
uspto-grants-2014_06
Patent number
US08748429B2

Reaction notes

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