Sodium hydride → 2-((1-((tert-Butyldimethylsilyl)oxy)-3-(5-(3-cyanophenyl)-1,3-dimethyl-2,4-dioxo-3,4-dihydro-1H-pyrrolo[3,4-d]pyrimidin-6(2H)-yl)propan-2-yl)oxy)-N-methoxy-N-methylacetamide

HRID 624575Notes

Reaction equation

HRID 624575 reaction equation
[Si:1]([O:8][CH2:9][CH:10]([OH:33])[CH2:11][N:12]1[C:20]([C:21]2[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=2)[C:24]#[N:25])=[C:19]2[C:14]([N:15]([CH3:32])[C:16](=[O:31])[N:17]([CH3:30])[C:18]2=[O:29])=[CH:13]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:37][C:38]([N:40]([O:42][CH3:43])[CH3:41])=[O:39]>C1COCC1>[Si:1]([O:8][CH2:9][CH:10]([O:33][CH2:37][C:38]([N:40]([O:42][CH3:43])[CH3:41])=[O:39])[CH2:11][N:12]1[C:20]([C:21]2[CH:28]=[CH:27][CH:26]=[C:23]([C:24]#[N:25])[CH:22]=2)=[C:19]2[C:14]([N:15]([CH3:32])[C:16](=[O:31])[N:17]([CH3:30])[C:18]2=[O:29])=[CH:13]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 108669612-Bromo-N-methoxy-N-methylacetamideHCID 867229013-(6-(3-((tert-Butyldimethylsilyl)oxy)-2-hydroxypropyl)-1,3-dimethyl-2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-5-yl)benzonitrile

Product 1

HCID 867229002-((1-((tert-Butyldimethylsilyl)oxy)-3-(5-(3-cyanophenyl)-1,3-dimethyl-2,4-dioxo-3,4-dihydro-1H-pyrrolo[3,4-d]pyrimidin-6(2H)-yl)propan-2-yl)oxy)-N-methoxy-N-methylacetamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 3-(6-(3-((tert-Butyldimethylsilyl)oxy)-2-hydroxypropyl)-1,3-dimethyl-2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-5-yl)benzonitrile (Example 9a, step 1) (280 mg, 0.597 mmol) in THF (5975 μL) was added sodium hydride (60% in mineral oil) (71.7 mg, 1.792 mmol) at 0° C. The resulting red solution was warmed to room temperature and stirred for 20 minutes, before being cooled to 0° C. 2-Bromo-N-methoxy-N-methylacetamide (Example 13, step 1) (141 mg, 0.777 mmol) was then added dropwise over 5 minutes. The reaction mixture was warmed to room temperature over 3 hours and then cooled to 0° C. and quenched with saturated aqueous ammonium chloride solution (5 mL). DCM (10 mL) was added to the biphasic solution. The aqueous phase was separated and extracted with DCM (3×10 mL); the combined organic extracts were dried (MgSO4) and concentrated under reduced pressure to afford a yellow oil. The oil was purified using Teledyne ISCO (12 g, SiO2) eluting with 0-65% EtOAc/hexanes to afford the title compound as an amorphous white solid.

Workup

  1. temperaturebefore being cooled to 0° C
  2. temperatureThe reaction mixture was warmed to room temperature over 3 hours
  3. temperaturecooled to 0° C.
  4. customquenched with saturated aqueous ammonium chloride solution (5 mL)
  5. additionDCM (10 mL) was added to the biphasic solution
  6. customThe aqueous phase was separated
  7. extractionextracted with DCM (3×10 mL)
  8. dry with materialthe combined organic extracts were dried (MgSO4)
  9. concentrationconcentrated under reduced pressure
  10. customto afford a yellow oil
  11. customThe oil was purified
  12. washeluting with 0-65% EtOAc/hexanes

Sources & evidence

ORD record
ord-9fc940ab2c174fa0bca988581a229c2b
Source dataset
uspto-grants-2016_04
Patent number
US09303035B2

Reaction notes

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