Methyl 3-(4-chloro-5,6,7,8-tetrahydro-[1]benzothieno[2,3-d]pyrimidin-2-yl)propionate → 3-[4-(Cyclopropyl-methyl-amino)-5,6,7,8-tetrahydro-[1]benzothiopheno[2,3-d]pyrimidin-2-yl]-propionic acid methyl ester

HRID 1056842Notes

Reaction equation

HRID 1056842 reaction equation
[CH3:1][O:2][C:3](=[O:20])[CH2:4][CH2:5][C:6]1[N:7]=[C:8](Cl)[C:9]2[C:14]3[CH2:15][CH2:16][CH2:17][CH2:18][C:13]=3[S:12][C:10]=2[N:11]=1.Cl.[CH:22]1([NH:25][CH3:26])[CH2:24][CH2:23]1>CO>[CH3:1][O:2][C:3](=[O:20])[CH2:4][CH2:5][C:6]1[N:7]=[C:8]([N:25]([CH:22]2[CH2:24][CH2:23]2)[CH3:26])[C:9]2[C:14]3[CH2:15][CH2:16][CH2:17][CH2:18][C:13]=3[S:12][C:10]=2[N:11]=1

Participants

4

Reactant 2

HCID 11001423Methyl 3-(4-chloro-5,6,7,8-tetrahydro-[1]benzothieno[2,3-d]pyrimidin-2-yl)propionateHCID 18546974N-methylcyclopropanamine hydrochloride

Product 1

HCID 897192803-[4-(Cyclopropyl-methyl-amino)-5,6,7,8-tetrahydro-[1]benzothiopheno[2,3-d]pyrimidin-2-yl]-propionic acid methyl esterYield 45.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The TEA (0.6 g, 0.0064 mol) was added dropwise at 10° C. to a mixture of 3-(4-chloro-5,6,7,8-tetrahydro-[1]benzothiopheno[2,3-d]pyrimidin-2-yl)-propionic acid methyl ester (1 g, 0.0032 mol) and cyclopropyl methyl amine hydrochloride (0.35 g, 0.0032 mol) in methanol (20 ml). The resulting mixture was stirred at R.T for 10 hrs. Methanol was removed and the reaction mixture was diluted with water and extracted with ethyl acetate (3×25 ml). The combined organic layers were dried over Na2SO4, concentrated and subjected to column purification on 60-120 silica using ethyl acetate (50%) in hexane to give 0.5 g (43%) of 3-[4-(cyclopropyl-methyl-amino)-5,6,7,8-tetrahydro-[1]benzothiopheno[2,3-d]pyrimidin-2-yl]-propionic acid methyl ester. 1H NMR (400 MHz, DMSO) δ ppm=0.35 (m, 2H), 0.72 (m, 2H), 1.69 (m, 2H), 1.85 (m, 2H), 2.77 (q, 4H), 2.86 (q, 2H), 2.9 (m, 1H), 2.97 (s, 3H) 3.02 (t, 2H), 3.56 (s, 3H). LC-MS: [M+H]=345.8.

Workup

  1. customMethanol was removed
  2. additionthe reaction mixture was diluted with water
  3. extractionextracted with ethyl acetate (3×25 ml)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated
  6. customsubjected to column purification on 60-120 silica

Sources & evidence

ORD record
ord-9ce31ec24d8246fdaef0d1b75f719d12
Source dataset
uspto-grants-2016_07
Patent number
US09399647B2

Reaction notes

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