Hydrochloric Acid → 2-(4-(Cyclopropyl(methyl)amino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-2-yl)acetic acid

HRID 1056834Notes

Reaction equation

HRID 1056834 reaction equation
[CH:1]1([N:4]([CH3:24])[C:5]2[C:6]3[C:19]4[CH2:20][CH2:21][CH2:22][CH2:23][C:18]=4[S:17][C:7]=3[N:8]=[C:9]([CH2:11][C:12]([O:14]CC)=[O:13])[N:10]=2)[CH2:3][CH2:2]1.O.[OH-].[Li+].Cl>C1COCC1.O>[CH:1]1([N:4]([CH3:24])[C:5]2[C:6]3[C:19]4[CH2:20][CH2:21][CH2:22][CH2:23][C:18]=4[S:17][C:7]=3[N:8]=[C:9]([CH2:11][C:12]([OH:14])=[O:13])[N:10]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 89714188Ethyl 2-(4-(cyclopropyl(methyl)amino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-2-yl)acetate

Product 1

HCID 897136992-(4-(Cyclopropyl(methyl)amino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-2-yl)acetic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 2-(4-(cyclopropyl(methyl)amino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-2-yl)acetate (1.0 gm, 0.00289 mol) in THF (9 ml) and water (1 ml) was added lithium hydroxide hydrate (0.24 gm, 0.00578 mol). The reaction mixture was stirred at room temperature for 16 h. After completion of the reaction, it was diluted with water. The aqueous layer was made acidic to pH 1 with 2N HCl and then extracted with ethyl acetate (25 ml×3). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated to get crude compound. It was purified by column chromatography by using 100-200 mesh silica gel and 2% MeOH: DCM as eluent to get 2-(4-(cyclopropyl(methyl)amino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-2-yl)acetic acid as an off white solid. Yield: (0.4 gm, 43.57%); 1H-NMR: (400 MHz, DMSO-d6); δ=12.46 (s, 1H), 3.70 (s, 2H), 2.99 (s, 3H), 2.96-2.91 (m, 1H), 2.90-2.87 (m, 2H), 2.83-2.80 (m, 2H), 1.88-1.84 (m, 2H), 1.71-1.66 (m, 2H), 0.78-0.65 (m, 2H), 0.43-0.31 (m, 2H); LC-MS [M+H]=317.9; HPLC purity=99.72%.

Workup

  1. customAfter completion of the reaction, it
  2. extractionextracted with ethyl acetate (25 ml×3)
  3. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto get crude compound
  7. customIt was purified by column chromatography

Sources & evidence

ORD record
ord-393641d4cf784f0c89a2cb06e1feea73
Source dataset
uspto-grants-2016_07
Patent number
US09399647B2

Reaction notes

Loading…