Methanol → HCID 70983874, compound

HRID 403345Notes

Reaction equation

HRID 403345 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][CH:18]=[C: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][N:16]=[C:11]2[C@H:10]1[NH:39]C(=O)OC(C)(C)C.FC(F)(F)C(O)=O.CO>C(Cl)Cl>[NH2:39][C@@H:10]1[C:11]2[C:12](=[N:13][CH:14]=[CH:15][N:16]=2)[C: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])=[CH: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

5

Reactant 3

HCID 887MethanolHCID 6422Trifluoroacetic acidHCID 71006810HCID 71006810, compound

Product 1

HCID 70983874HCID 70983874, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

In a 50 mL round-bottomed flask was dissolved tert-butyl (5S,6S)-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-dihydro-5H-cyclohepta[b]pyrazin-5-ylcarbamate (58.6 mg, 0.093 mmol) in methylene chloride (1 mL). trifluoroacetic acid (0.5 mL) was added, and the mixture was stirred at rt for 1 h. LCMS showed complete conversion. Volatile components 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 (36 mg, 73%) as a tan solid: MS (ESI)[M+H+]=532.3; 1H NMR (400 MHz, CDCl3) δ 8.47 (ddd, J=11.4, 8.1, 2.5 Hz, 2H), 8.07 (d, J=5.1 Hz, 1H), 7.46 (t, J=6.7 Hz, 1H), 7.30 (d, J=7.9 Hz, 1H), 7.20 (d, J=7.1 Hz, 1H), 7.08 (dt, J=14.8, 7.7 Hz, 2H), 6.99 (td, J=8.2, 5.3 Hz, 2H), 6.41 (dt, J=22.6, 7.2 Hz, 1H), 4.90-4.68 (m, 2H), 4.56 (dd, J=17.3, 12.7 Hz, 1H), 4.15 (ddd, J=24.9, 20.2, 15.2 Hz, 2H), 3.83 (dt, J=7.2, 6.4 Hz, 1H), 3.64 (dd, J=33.2, 16.2 Hz, 1H), 3.26 (t, J=13.1 Hz, 1H), 2.69 (dd, J=28.5, 13.4 Hz, 1H), 2.39 (d, J=6.8 Hz, 2H), 2.33-2.05 (m, 3H), 2.03-1.69 (m, 2H); 19F NMR (376 MHz, CDCl3) δ −137.26-−138.00 (m), −142.22 (dd, J=96.1, 21.6 Hz).

Workup

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

Sources & evidence

ORD record
ord-6841ec960f06424da8841e3871dc4b62
Source dataset
uspto-grants-2014_06
Patent number
US08748429B2

Reaction notes

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