Sodium hydride → 10-(5-Chlorofuran-2-yl)-1,3-dimethyl-5-(4-methylthiazol-2-yl)-8-((2-oxopyrrolidin-1-yl)methyl)-7,8-dihydro-1H-pyrimido[4',5':3,4]pyrrolo[2,1-c][1,4]oxazine-2,4(3H,10H)-dione

HRID 624584Notes

Reaction equation

HRID 624584 reaction equation
[H-].[Na+].Br[CH2:4][CH2:5][CH2:6][C:7]([NH:9][CH2:10][CH:11]1[O:16][CH:15]([C:17]2[O:18][C:19]([Cl:22])=[CH:20][CH:21]=2)[C:14]2=[C:23]3[N:35]([CH3:36])[C:34](=[O:37])[N:33]([CH3:38])[C:32](=[O:39])[C:24]3=[C:25]([C:26]3[S:27][CH:28]=[C:29]([CH3:31])[N:30]=3)[N:13]2[CH2:12]1)=[O:8]>C1COCC1>[Cl:22][C:19]1[O:18][C:17]([CH:15]2[C:14]3=[C:23]4[N:35]([CH3:36])[C:34](=[O:37])[N:33]([CH3:38])[C:32](=[O:39])[C:24]4=[C:25]([C:26]4[S:27][CH:28]=[C:29]([CH3:31])[N:30]=4)[N:13]3[CH2:12][CH:11]([CH2:10][N:9]3[CH2:4][CH2:5][CH2:6][C:7]3=[O:8])[O:16]2)=[CH:21][CH:20]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 867229094-Bromo-N-((10-(5-chlorofuran-2-yl)-1,3-dimethyl-5-(4-methylthiazol-2-yl)-2,4-dioxo-2,3,4,7,8,10-hexahydro-1H-pyrimido[4',5':3,4]pyrrolo[2,1-c][1,4]oxazin-8-yl)methyl)butanamide

Product 1

HCID 7628489110-(5-Chlorofuran-2-yl)-1,3-dimethyl-5-(4-methylthiazol-2-yl)-8-((2-oxopyrrolidin-1-yl)methyl)-7,8-dihydro-1H-pyrimido[4',5':3,4]pyrrolo[2,1-c][1,4]oxazine-2,4(3H,10H)-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (60% wt in mineral oil, 26.8 mg, 0.671 mmol) was added to a solution of 4-bromo-N-((10-(5-chlorofuran-2-yl)-1,3-dimethyl-5-(4-methylthiazol-2-yl)-2,4-dioxo-2,3,4,7,8,10-hexahydro-1H-pyrimido[4′,5′:3,4]pyrrolo[2,1-c][1,4]oxazin-8-yl)methyl)butanamide (82 mg, 0.134 mmol) in THF (6711 μl). The mixture was heated at reflux for 1 hour, then cooled to room temperature and quenched with water (30 ml). The mixture was extracted with ethyl acetate (2×30 ml). The combined organic extracts were washed with brine, passed through a hydrophobic frit and evaporated under vacuum to afford the title compound as a mixture of diastereomers.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 1 hour
  3. customquenched with water (30 ml)
  4. extractionThe mixture was extracted with ethyl acetate (2×30 ml)
  5. washThe combined organic extracts were washed with brine
  6. customevaporated under vacuum

Sources & evidence

ORD record
ord-92a7d2e834df459d9f2cac3cfb4e20a8
Source dataset
uspto-grants-2016_04
Patent number
US09303035B2

Reaction notes

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