Diisobutylaluminumhydride → 2-{5-Phenyl-4-[(pyridin-2-ylmethyl)amino]thieno[2,3-d]pyrimidin-2-yl}propane-1,3-diol

HRID 910195Notes

Reaction equation

HRID 910195 reaction equation
C([O:3][C:4](=O)[CH:5]([C:11]1[N:12]=[C:13]([NH:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=2)[C:14]2[C:19]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:18][S:17][C:15]=2[N:16]=1)[C:6](OCC)=[O:7])C.[H-].C([Al+]CC(C)C)C(C)C>O1CCCC1>[C:20]1([C:19]2[C:14]3[C:13]([NH:26][CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=4)=[N:12][C:11]([CH:5]([CH2:6][OH:7])[CH2:4][OH:3])=[N:16][C:15]=3[S:17][CH:18]=2)[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

4

Reactant 2

HCID 21225700DiisobutylaluminumhydrideHCID 673819232-{5-Phenyl-4-[(pyridin-2-ylmethyl)amino]thieno[2,3-d]pyrimidin-2-yl}malonic acid diethyl ester

Product 1

HCID 114179512-{5-Phenyl-4-[(pyridin-2-ylmethyl)amino]thieno[2,3-d]pyrimidin-2-yl}propane-1,3-diolYield 30.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of 2-{5-phenyl-4-[(pyridin-2-ylmethyl)amino]thieno[2,3-d]pyrimidin-2-yl}malonic acid diethyl ester (0.32 g, 0.672 mmol) in anhydrous tetrahydrofuran (10 ml) was cooled in an ice-bath and treated, under a nitrogen atmosphere, with diisobutylaluminium hydride (1M solution in hexane, 5.52 ml, 5.52 mmol) over 15 minutes. The reaction mixture was allowed to warm up and left to stir at ambient temperature for 3 hours. The resultant mixture was then cooled in an ice-bath and quenched by the slow addition of methanol (5 ml) followed by water (10 ml). The mixture was then diluted with 2M sodium hydroxide solution (50 ml) and extracted with ethyl acetate (3×50 ml). The combined organic extracts were dried (MgSO4) and the solvent removed in vacuo to give the crude product. Purification by flash chromatography (silica) eluting with 5% methanol in dichloromethane gave 2-{5-phenyl-4-[(pyridin-2-ylmethyl)amino]thieno[2,3-d]pyrimidin-2-yl}propane-1,3-diol as a pale yellow solid (0.08 g), m.p. 137°-139° C.

Workup

  1. temperatureto warm up
  2. waitleft
  3. customquenched by the slow addition of methanol (5 ml)
  4. additionThe mixture was then diluted with 2M sodium hydroxide solution (50 ml)
  5. extractionextracted with ethyl acetate (3×50 ml)
  6. dry with materialThe combined organic extracts were dried (MgSO4)
  7. customthe solvent removed in vacuo
  8. customto give the crude product
  9. customPurification by flash chromatography (silica)
  10. washeluting with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-59a58506a8ae4efa9742f12e35b14164
Source dataset
uspto-grants-2011_09
Patent number
US08022076B2

Reaction notes

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