HCID 67160330, compound → HCID 45107957, compound

HRID 2362024Notes

Reaction equation

HRID 2362024 reaction equation
[C:1](=[O:47])([O:35][CH2:36][CH2:37][CH2:38][O:39]CC1C=CC=CC=1)[O:2][CH2:3][O:4][C:5]1[C:6](=[O:34])[C:7]([C:22]([NH:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=2[F:33])=[O:23])=[CH:8][N:9]2[CH2:14][C@H:13]3[N:15]4[CH2:20][CH2:19][CH2:18][C@@H:16]4[CH2:17][N:12]3[C:11](=[O:21])[C:10]=12>CO.CC(O)=O.[Pd]>[C:1](=[O:47])([O:35][CH2:36][CH2:37][CH2:38][OH:39])[O:2][CH2:3][O:4][C:5]1[C:6](=[O:34])[C:7]([C:22]([NH:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=2[F:33])=[O:23])=[CH:8][N:9]2[CH2:14][C@H:13]3[N:15]4[CH2:20][CH2:19][CH2:18][C@@H:16]4[CH2:17][N:12]3[C:11](=[O:21])[C:10]=12

Participants

4

Reactant 1

HCID 67160330HCID 67160330, compound

Product 1

HCID 45107957HCID 45107957, compoundYield 99%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 10129899Acetic acid methanolSolvent

Procedure

A solution of {[(4aS,13aR)-8-({[(2,4-difluorophenyl)methyl]amino}carbonyl)-9,11-dioxo-2,3,4a,5,9,11,13,13a-octahydro-1H-pyrido[1,2-a]pyrrolo[1′,2′:3,4]imidazo[1,2-d]pyrazin-10-yl]oxy}methyl 3-[(phenylmethyl)oxy]propyl carbonate (2.30 g, 3.52 mmol) in 50 mL of 1:1 MeOH/AcOH was subjected to hydrogenation at 55 psi in the presence of 0.75 g of 10% palladium on charcoal. After 5 hours the reaction vessel was purged with nitrogen, catalyst removed by filtration through celite and the filtrate concentrated to dryness at reduced pressure. The residue was dissolved in dichloromethane and the solution mixed with saturated aqueous sodium bicarbonate. The mixture was stirred vigorously for 25 minutes and the phases separated. The aqueous phase was extracted with one additional portion of dichloromethane. The combined dichloromethane solutions were washed with saturated aqueous brine, dried over sodium sulfate and concentrated to dryness at reduced pressure to give the title compound (1.96 g, 99%) as a light tan foam. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 10.18 (t, J=5.8 Hz, 1 H), 8.39 (s, 1 H), 7.37-7.26 (m, 1 H), 6.84-6.72 (m, 2 H), 5.93 (d, J=6.6 Hz, 1 H), 5.85 (d, J=6.6 Hz, 1 H), 4.66-4.36 (m, 4 H), 4.34-4.10 (m, 3 H), 3.87 (t, J=11.3 Hz, 1 H), 3.79-3.64 (m, 3 H), 3.17-3.02 (m, 2 H), 2.90-2.74 (m, 2 H), 2.11-1.81 (m, 4 H), 1.71-1.57 (m, 2 H): ES+ MS: 563 (M+1).

Workup

  1. customAfter 5 hours the reaction vessel was purged with nitrogen, catalyst
  2. customremoved by filtration through celite
  3. concentrationthe filtrate concentrated to dryness at reduced pressure
  4. dissolutionThe residue was dissolved in dichloromethane
  5. additionthe solution mixed with saturated aqueous sodium bicarbonate
  6. customthe phases separated
  7. extractionThe aqueous phase was extracted with one additional portion of dichloromethane
  8. washThe combined dichloromethane solutions were washed with saturated aqueous brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated to dryness at reduced pressure

Sources & evidence

ORD record
ord-b04442bc55e94efba76fcc74f691944f
Source dataset
uspto-grants-2014_04
Patent number
US08691823B2

Reaction notes

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