Sodium hydride → HCID 77107830, compound

HRID 2201267Notes

Reaction equation

HRID 2201267 reaction equation
[H-].[Na+].Cl[CH2:4][CH2:5][O:6][C:7](=[O:39])[NH:8][CH2:9][CH:10]1[S:15][CH:14]([C:16]2[O:17][C:18]([Cl:21])=[CH:19][CH:20]=2)[C:13]2=[C:22]3[N:34]([CH3:35])[C:33](=[O:36])[N:32]([CH3:37])[C:31](=[O:38])[C:23]3=[C:24]([C:25]3[S:26][CH:27]=[C:28]([CH3:30])[N:29]=3)[N:12]2[CH2:11]1>C1COCC1>[Cl:21][C:18]1[O:17][C:16]([CH:14]2[C:13]3=[C:22]4[N:34]([CH3:35])[C:33](=[O:36])[N:32]([CH3:37])[C:31](=[O:38])[C:23]4=[C:24]([C:25]4[S:26][CH:27]=[C:28]([CH3:30])[N:29]=4)[N:12]3[CH2:11][CH:10]([CH2:9][N:8]3[CH2:4][CH2:5][O:6][C:7]3=[O:39])[S:15]2)=[CH:20][CH:19]=1

Participants

4

Reactant 2

HCID 24758Sodium hydride2×HCID 86723507HCID 86723507, compound

Product 1

HCID 77107830HCID 77107830, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (60% wt in mineral oil, 6.69 mg, 0.167 mmol) was added to a solution of 2-chloroethyl((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]thiazin-8-yl)methyl)carbamate (48.9 mg, 0.084 mmol) in THF (4 mL). The mixture was heated at reflux for 18 hours. A further portion of sodium hydride (60% wt in mineral oil, 33.4 mg, 0.836 mmol) was added and the mixture heated at reflux for a further 2 days. The mixture was cooled to room temperature, quenched with water (20 ml) and extracted with ethyl acetate (2×30 ml). The combined organic extracts were washed with brine, passed through a hydrophobic frit and evaporated under vacuum. Purification by mass-directed HPLC under the following conditions afforded the title compound as a mixture of diastereomers.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 18 hours
  3. temperaturethe mixture heated
  4. temperatureat reflux for a further 2 days
  5. customquenched with water (20 ml)
  6. extractionextracted with ethyl acetate (2×30 ml)
  7. washThe combined organic extracts were washed with brine
  8. customevaporated under vacuum
  9. customPurification by mass-directed HPLC under the following conditions

Sources & evidence

ORD record
ord-5a49e539ae5f4ce3a3f4a7f8d4190592
Source dataset
uspto-grants-2016_06
Patent number
US09359381B2

Reaction notes

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