Pyridine → HCID 67369218, compound

HRID 1910908Notes

Reaction equation

HRID 1910908 reaction equation
[C:1](Cl)(=[O:5])[C:2](Cl)=O.CN([CH:10]=[O:11])C.[Si:12]([O:19][CH2:20][C:21]1[N:25]2[CH2:26][C:27]3([C:34]4[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][CH:35]=4)[NH:33][CH2:32][CH2:31][N:28]3[C:29](=[O:30])[C:24]2=[CH:23][CH:22]=1)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13].[N:41]1C=CC=[CH:43][CH:42]=1>C(Cl)Cl>[C:15]([Si:12]([CH3:13])([CH3:14])[O:19][CH2:20][C:21]1[N:25]2[CH2:26][C:27]3([C:34]4[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][CH:35]=4)[N:33]([C:10]([C:2]4[C:42]([CH3:43])=[N:41][O:5][CH:1]=4)=[O:11])[CH2:32][CH2:31][N:28]3[C:29](=[O:30])[C:24]2=[CH:23][CH:22]=1)([CH3:18])([CH3:16])[CH3:17]

Participants

6

Reactant 4

HCID 1049PyridineHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 67368676HCID 67368676, compound

Product 1

HCID 67369218HCID 67369218, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To generate the acid chloride 3-methyl-1,2-oxazole-4-carboxylic acid (100 mg, 0.79 mmol) was dissolved in CH2Cl2 (10 mL). Oxalyl chloride (0.6 mL, 2.75 mmol) and a drop of DMF were added at 0° C. The ice bath was removed and the mixture stirred for 1 h before the solvent and excess of oxalyl chloride were removed with a strong stream of nitrogen. The residue was further dried in vacuo. 8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-10a-(4-chlorophenyl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (85 mg, 0.20 mmol) was dissolved in pyridine (4 mL) and the solution added to the previously generated acyl chloride in pyrine (1 mL) at 0° C. The ice bath was removed after 15 min and the mixture stirred at room temperature until completion (18 h). The resulting suspension was concentrated in vacuo and the residue partitioned between CH2Cl2 (20 mL) and a saturated aqueous solution of NaHCO3 (10 mL). The organic layers were separated and washed further with a saturated aqueous solution of NaHCO3 (10 mL) and brine (5 mL), dried (MgSO4), filtered and concentrated in vacuo to give a yellow gum. This gum was purified by flash column chromatography (Biotage SP4, 12 g cartridge, 70-100% EtOAc gradient in n-hexanes) to give 8-({[tert butyl(dimethyl)silyl]oxy}methyl)-10a-(4-chlorophenyl)-1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one as a pale yellow solid (76 mg, yield 71%). 1H NMR (400 MHz, MeOD): δ 0.11 (d, 6H, J 6.9 Hz), 0.90 (s, 9H), 2.35 (s, 3H), 3.78 (dt, 1H, J 11.5, 8.0 Hz), 4.05-4.21 (m, 2H), 4.31 (ddd, 1H, J 11.6, 8.5, 3.9 Hz), 4.46 (d, 1H, J 13.2 Hz), 4.65-4.77 (m, 2H), 5.96 (d, 1H, J 13.2 Hz), 6.16 (d, 1H, J 3.9 Hz), 6.77 (d, 1H, J 3.9 Hz), 7.26-7.32 (m, 2H), 7.38-7.43 (m, 2H), 9.10 (s, 1H).

Workup

  1. customThe ice bath was removed
  2. customwere removed with a strong stream of nitrogen
  3. customThe residue was further dried in vacuo
  4. customThe ice bath was removed after 15 min
  5. stirringthe mixture stirred at room temperature until completion (18 h)
  6. concentrationThe resulting suspension was concentrated in vacuo
  7. customthe residue partitioned between CH2Cl2 (20 mL)
  8. customThe organic layers were separated
  9. washwashed further with a saturated aqueous solution of NaHCO3 (10 mL) and brine (5 mL)
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customto give a yellow gum
  14. customThis gum was purified by flash column chromatography (Biotage SP4, 12 g cartridge, 70-100% EtOAc gradient in n-hexanes)

Sources & evidence

ORD record
ord-b43ec7a4ed2945e5bc61f7fd1b2d7482
Source dataset
uspto-grants-2013_12
Patent number
US08604034B2

Reaction notes

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