Diisopropyl Ether → HCID 86698058, compound

HRID 518903Notes

Reaction equation

HRID 518903 reaction equation
[OH:1][CH2:2][C:3]1[S:11][C:10]2[CH:9]=[N:8][C:7]([N:12](CO)[C:13]3[CH:18]=[C:17]([CH3:19])[C:16]([N:20]4[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]4)=[CH:15][C:14]=3[O:27][CH:28]([CH3:30])[CH3:29])=[N:6][C:5]=2[C:4]=1[C:33]1[C:34]([O:40][CH3:41])=[N:35][C:36]([CH3:39])=[CH:37][CH:38]=1.C(OC(C)C)(C)C.CCCCC>C1COCC1.[OH-].[Na+].C(OCC)(=O)C.O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C(#N)C>[CH3:41][O:40][C:34]1[C:33]([C:4]2[C:5]3[N:6]=[C:7]([NH:12][C:13]4[CH:18]=[C:17]([CH3:19])[C:16]([N:20]5[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]5)=[CH:15][C:14]=4[O:27][CH:28]([CH3:29])[CH3:30])[N:8]=[CH:9][C:10]=3[S:11][C:3]=2[CH2:2][OH:1])=[CH:38][CH:37]=[C:36]([CH3:39])[N:35]=1

Participants

10

Reactant 3

HCID 7914Diisopropyl EtherHCID 8003PentaneHCID 86698059HCID 86698059, compound

Product 1

HCID 86698058HCID 86698058, compoundYield 40.9%

Reagents, catalysts & solvents 6

HCID 311Citric AcidSolventHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Procedure

A solution of 457 mg of the {[6-(hydroxymethyl)-7-(2-methoxy-6-methylpyridin-3-yl)thieno[3,2-d]pyrimidin-2-yl][5-methyl-4-(4-methylpiperazin-1-yl)-2-(propan-2-yloxy)phenyl]amino}methanol mixture in 30 ml of THF and 4.75 ml of 1 M sodium hydroxide is stirred at ambient temperature for 2 h 15. The mixture is diluted with 80 ml of ethyl acetate, 40 ml of water and 5 ml of an aqueous 10% citric acid solution. The aqueous phase is extracted three times with 40 ml of ethyl acetate. The organic phases are washed with 50 ml of a saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated under vacuum. The crude product is purified on 25 g of silica, elution being carried out with 1-5% of methanol (containing 10% by volume of 28% ammonium hydroxide) in dichloromethane, so as to obtain a brown oil. Placing the oil in solution in 1 ml of acetonitrile and adding diisopropyl ether and pentane gives a suspension which is concentrated under vacuum. After trituration with pentane, the resulting solid is filtered off and dried under vacuum, so as to obtain 177 mg of [7-(2-methoxy-6-methylpyridin-3-yl)-2-{[5-methyl-4-(4-methylpiperazin-1-yl)-2-(propan-2-yloxy)phenyl]amino}thieno[3,2-d]pyrimidin-6-yl]methanol in the form of a beige solid.

Workup

  1. extractionThe aqueous phase is extracted three times with 40 ml of ethyl acetate
  2. washThe organic phases are washed with 50 ml of a saturated sodium chloride solution
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe crude product is purified on 25 g of silica, elution
  7. customso as to obtain a brown oil
  8. customgives a suspension which
  9. concentrationis concentrated under vacuum
  10. filtrationAfter trituration with pentane, the resulting solid is filtered off
  11. customdried under vacuum

Sources & evidence

ORD record
ord-7c85cfea21ec4a789a909f242ff49170
Source dataset
uspto-grants-2015_08
Patent number
US09115140B2

Reaction notes

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