Hydrochloric Acid → 3-[4-(Cyclopropyl-methyl-amino)-5,6,7,8-tetrahydro-[1]benzothiopheno[2,3-d]pyrimidin-2-yl]-propionic acid

HRID 1056843Notes

Reaction equation

HRID 1056843 reaction equation
[Li+].[OH-].C[O:4][C:5](=[O:26])[CH2:6][CH2:7][C:8]1[N:9]=[C:10]([N:21]([CH:23]2[CH2:25][CH2:24]2)[CH3:22])[C:11]2[C:16]3[CH2:17][CH2:18][CH2:19][CH2:20][C:15]=3[S:14][C:12]=2[N:13]=1.Cl>O.C1COCC1>[CH:23]1([N:21]([CH3:22])[C:10]2[C:11]3[C:16]4[CH2:17][CH2:18][CH2:19][CH2:20][C:15]=4[S:14][C:12]=3[N:13]=[C:8]([CH2:7][CH2:6][C:5]([OH:26])=[O:4])[N:9]=2)[CH2:24][CH2:25]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 897192803-[4-(Cyclopropyl-methyl-amino)-5,6,7,8-tetrahydro-[1]benzothiopheno[2,3-d]pyrimidin-2-yl]-propionic acid methyl ester

Product 1

HCID 716677593-[4-(Cyclopropyl-methyl-amino)-5,6,7,8-tetrahydro-[1]benzothiopheno[2,3-d]pyrimidin-2-yl]-propionic acidYield 54%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

The LiOH (0.047 g, 0.0018 mol) dissolved in water (2 ml) was added to a solution of 3-[4-(cyclopropyl-methyl-amino)-5,6,7,8-tetrahydro-[1]benzothiopheno[2,3-d]pyrimidin-2-yl]-propionic acid methyl ester (0.5 g, 0.0014 mol) in THF (3 ml), and the resulting solution was stirred at R.T for 3 hrs. The reaction mixture was diluted with water, acidified with dilute HCl (up to pH 5) and extracted with ethyl acetate (3×15 ml). The combined organic layers were dried over Na2SO4, concentrated, and the crude was purified by preparative HPLC to give 0.25 g (54%) of 3-[4-(cyclopropyl-methyl-amino)-5,6,7,8-tetrahydro-[1]benzothiopheno[2,3-d]pyrimidin-2-yl]-propionic acid. 1H NMR (400 MHz, CDCl3) δ ppm=0.53 (m, 2H), 0.87 (m, 2H), 1.76 (m, 2H), 1.92 (m, 2H), 2.84 (m, 7H), 3.1 (s, 3H), 3.22 (t, 2H), 14.75 (s, 1H). LC-MS: [M+H]=331.9.

Workup

  1. extractionextracted with ethyl acetate (3×15 ml)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. concentrationconcentrated
  4. customthe crude was purified by preparative HPLC

Sources & evidence

ORD record
ord-6e3c6c5c45b446c49aba85104af4286a
Source dataset
uspto-grants-2016_07
Patent number
US09399647B2

Reaction notes

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