Sodium hydride → 2-Chloro-6-cyclopropyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine

HRID 528475Notes

Reaction equation

HRID 528475 reaction equation
[CH:1]1([CH:4]([O:7][C:8]2[C:9](Cl)=[N:10][C:11]([Cl:20])=[N:12][C:13]=2[N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[CH2:5][OH:6])[CH2:3][CH2:2]1.[H-].[Na+]>C1COCC1>[Cl:20][C:11]1[N:12]=[C:13]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:8]2[O:7][CH:4]([CH:1]3[CH2:3][CH2:2]3)[CH2:5][O:6][C:9]=2[N:10]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 867117572-Cyclopropyl-2-(2,4-dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-ethanol

Product 1

HCID 867117582-Chloro-6-cyclopropyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-cyclopropyl-2-(2,4-dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-ethanol (215 mg, 0.64 mmol) in THF (10 mL) was added sodium hydride (71 mg, 1.93 mmol, 65% dispersion in mineral oil) and the reaction stirred for 2 hours. The reaction was quenched with saturated aqueous ammonium chloride solution (15 mL) and water (5 mL) then extracted with ethyl acetate (3×20 mL). The combined organic phases were washed with brine (15 mL), dried (Na2SO4) then concentrated in vacuo to give 2-Chloro-6-cyclopropyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine as a white solid (191 mg, quantitative). LCMS: RT=3.18 min, [M+H]+=298/300.

Workup

  1. customThe reaction was quenched with saturated aqueous ammonium chloride solution (15 mL) and water (5 mL)
  2. extractionthen extracted with ethyl acetate (3×20 mL)
  3. washThe combined organic phases were washed with brine (15 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationthen concentrated in vacuo

Sources & evidence

ORD record
ord-959dad88bebc4397978e8d51dece1d21
Source dataset
uspto-grants-2016_05
Patent number
US09346817B2

Reaction notes

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