Lithium hydroxide, monohydrate → [4-(Cyclopropyl-methyl-amino)-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d]pyrimidin-2-yl]-methanol

HRID 1056850Notes

Reaction equation

HRID 1056850 reaction equation
[CH:1]1([N:4]([CH3:23])[C:5]2[C:6]3[C:18]4[CH2:19][CH2:20][CH2:21][CH2:22][C:17]=4[S:16][C:7]=3[N:8]=[C:9]([CH2:11][O:12]C(=O)C)[N:10]=2)[CH2:3][CH2:2]1.O.[OH-].[Li+]>C1COCC1.O>[CH:1]1([N:4]([CH3:23])[C:5]2[C:6]3[C:18]4[CH2:19][CH2:20][CH2:21][CH2:22][C:17]=4[S:16][C:7]=3[N:8]=[C:9]([CH2:11][OH:12])[N:10]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 118129690HCID 118129690, compound

Product 1

HCID 71667761[4-(Cyclopropyl-methyl-amino)-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d]pyrimidin-2-yl]-methanolYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of acetic acid 4-(cyclopropyl-methyl-amino)-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d]pyrimidin-2-ylmethyl ester (4 g, 0.012 mol) in THF (10 ml) and water (5 ml) was added lithium hydroxide monohydrate (1.48 g, 0.036 mol). The solution stirred at room temperature for 4 h. The volatiles were removed by distillation, and the residue was diluted with water, and extracted with ethyl acetate (3×25 ml). The combined organic layers were dried over anhydrous sodium sulphate, concentrated, and purified by chromatography on 60-120 silica gel using 25%-ethyl acetate in hexane to give the desired product [4-(cyclopropyl-methyl-amino)-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d]pyrimidin-2-yl]-methanol (2.5 g, 72%) as off-white solid. 1H NMR (400 MHz, CDCl3): δ 0.45-0.50 (m, 2H), 0.72-0.80 (m, 2H), 1.72-1.80 (m, 2H), 1.88-1.94 (m, 2H), 2.82-2.94 (m, 5H), 3.07 (s, 3H), 3.94 (t, 1H), 4.70 (d, 2H); LC-MS: [M+H]=290.0 m/z.

Workup

  1. customThe volatiles were removed by distillation
  2. additionthe residue was diluted with water
  3. extractionextracted with ethyl acetate (3×25 ml)
  4. dry with materialThe combined organic layers were dried over anhydrous sodium sulphate
  5. concentrationconcentrated
  6. custompurified by chromatography on 60-120 silica gel using 25%-ethyl acetate in hexane

Sources & evidence

ORD record
ord-b808532f4ac74818b7df28eeaf53dfd2
Source dataset
uspto-grants-2016_07
Patent number
US09399647B2

Reaction notes

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