Methanol → HCID 70984207, compound

HRID 403350Notes

Reaction equation

HRID 403350 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]([NH:20][C:21]([N:23]2[CH2:28][CH2:27][CH:26]([N:29]3[C:37]4[C:32](=[N:33][CH:34]=[CH:35][CH:36]=4)[N:31](COCC[Si](C)(C)C)[C:30]3=[O:46])[CH2:25][CH2:24]2)=[O:22])[C:12]2=[N:13][CH:14]=[CH:15][N:16]=[C:11]2[C@H:10]1[NH:47]C(=O)OC(C)(C)C.FC(F)(F)C(O)=O.CO>C(Cl)Cl>[NH2:47][C@@H:10]1[C:11]2=[N:16][CH:15]=[CH:14][N:13]=[C:12]2[C@H:17]([NH:20][C:21]([N:23]2[CH2:24][CH2:25][CH:26]([N:29]3[C:37]4[C:32](=[N:33][CH:34]=[CH:35][CH:36]=4)[NH:31][C:30]3=[O:46])[CH2:27][CH2:28]2)=[O:22])[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

5

Reactant 3

HCID 887MethanolHCID 6422Trifluoroacetic acidHCID 71006872HCID 71006872, compound

Product 1

HCID 70984207HCID 70984207, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

In a 50 mL round-bottomed flask was dissolved tert-butyl (5S,6S,9R)-6-(2,3-difluorophenyl)-9-(4-(2-oxo-3-((2-(trimethylsilyl)ethoxy)methyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamido)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyrazin-5-ylcarbamate (31 mg, 0.041 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 1.5 h: LCMS showed complete conversion. The solvent was 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 (12 mg, 55%) as a white solid: MS (ESI) [M+H]+=535.3; 1H NMR (400 MHz, CDCl3) δ 10.98-9.87 (m, 1H), 8.56 (d, J=2.5 Hz, 1H), 8.42 (d, J=2.5 Hz, 1H), 8.07 (dd, J=5.3, 1.2 Hz, 1H), 7.35 (dd, J=7.9, 1.2 Hz, 1H), 7.21-7.05 (m, 4H), 6.98 (dd, J=7.9, 5.3 Hz, 1H), 5.29 (dd, J=10.4, 5.1 Hz, 1H), 4.71-4.55 (m, 2H), 4.35 (d, J=13.6 Hz, 2H), 3.05 (1, J=13.0 Hz, 2H), 2.94 (t, J=9.3 Hz, 1H), 2.53 (t, J=11.7 Hz, 2H), 2.41-2.23 (m, 2H), 2.16-1.69 (m, 6H); 19F NMR (376 MHz, CDCl3) δ −137.32 (ddd, J=21.4, 9.6, 4.5 Hz), −142.66 (d, J=19.5 Hz).

Workup

  1. customto give a colorless solution
  2. customThe solvent was 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-a54cee84186b4fa7bbcef2649bb7d567
Source dataset
uspto-grants-2014_06
Patent number
US08748429B2

Reaction notes

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