Hydrochloric Acid → ((1S)-5-{3-[[2-(4-ethylphenyl)-5-methyl-4-pyrimidinyl](methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetic acid

HRID 603486Notes

Reaction equation

HRID 603486 reaction equation
[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]([N:15]([CH3:35])[CH2:16][CH2:17][CH2:18][O:19][C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=3)[C@H:25]([CH2:29][C:30]([O:32]CC)=[O:31])[CH2:24][CH2:23]4)[C:12]([CH3:36])=[CH:11][N:10]=2)=[CH:5][CH:4]=1)[CH3:2].O.[Li+].[OH-].Cl>C1COCC1.CCO>[CH2:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]2[N:14]=[C:13]([N:15]([CH3:35])[CH2:16][CH2:17][CH2:18][O:19][C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=3)[C@H:25]([CH2:29][C:30]([OH:32])=[O:31])[CH2:24][CH2:23]4)[C:12]([CH3:36])=[CH:11][N:10]=2)=[CH:7][CH:8]=1)[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 3939Lithium HydroxideHCID 59300499ethyl ((1S)-5-{3-[[2-(4-ethylphenyl)-5-methyl-4-pyrimidinyl](methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

Product 1

HCID 10411897((1S)-5-{3-[[2-(4-ethylphenyl)-5-methyl-4-pyrimidinyl](methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetic acidYield 89%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl ((1S)-5-{3-[[2-(4-ethylphenyl)-5-methyl-4-pyrimidinyl](methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate (Example 343, 140 mg, 0.290 mmol) in a mixture of THF (5 mL), water (5 mL), and EtOH (2.5 mL) was added LiOH (27.5 mg, 1.15 mmol). After vigorously stirring for 24 h, the reaction mixture was acidified to pH ˜5 using HCl (1 N aqueous solution) and extracted with CH2Cl2. The combined organic layers were dried (Na2SO4), filtered, and then concentrated under reduced pressure to give the product (118 mg, 89%) as a white foam. 1H NMR (400 MHz, acetone-d6) δ 1.26 (t, 3H), 1.70-1.76 (m, 1H), 2.18-2.21 (m, 2H), 2.37 (s, 3H), 2.33-2.42 (m, 2H), 2.67-2.85 (m, 5H), 3.28 (s, 3H), 3.44-3.45 (m, 1H), 3.86 (t, 2H), 4.07 (t, 2H), 6.71 (d, 1H), 6.78 (s, 1H), 7.12 (d, 1H), 7.27 (d, 2H), 8.08 (s, 1H), 8.35 (d, 2H); LC-MS: RT=2.53 min, (M+H)+ 460.4.

Workup

  1. extractionextracted with CH2Cl2
  2. dry with materialThe combined organic layers were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-02f8da3492ac4ac0a6e6669276d2bb40
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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