Lithium hydroxide, monohydrate → HCID 9916306, compound

HRID 275883Notes

Reaction equation

HRID 275883 reaction equation
C([O:3][C:4](=[O:44])[CH2:5][CH2:6][N:7]([C:17](=[O:43])[CH2:18][N:19]([C:21](=[O:42])[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([NH:29][C:30]([NH:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=2[CH3:39])=[O:31])=[C:25]([O:40][CH3:41])[CH:24]=1)[CH3:20])[CH2:8][CH2:9][CH2:10][N:11]1[CH2:15][CH2:14][CH2:13][C:12]1=[O:16])C.O.[OH-].[Li+]>O1CCCC1.O>[CH3:41][O:40][C:25]1[CH:24]=[C:23]([CH2:22][C:21]([N:19]([CH2:18][C:17]([N:7]([CH2:8][CH2:9][CH2:10][N:11]2[CH2:15][CH2:14][CH2:13][C:12]2=[O:16])[CH2:6][CH2:5][C:4]([OH:44])=[O:3])=[O:43])[CH3:20])=[O:42])[CH:28]=[CH:27][C:26]=1[NH:29][C:30]([NH:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[CH3:39])=[O:31]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 69679736HCID 69679736, compound

Product 1

HCID 9916306HCID 9916306, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of ({[3-methoxy-4-(3-o-tolylureido)phenyl]-acetyl}-N-methylamino)-acetic acid [0.80 g, Reference Example 1] and 3-[3-(2-oxo-pyrrolidin-1-yl)-prop-l1ylamino]-propionic acid ethyl ester (0.51 g, Reference Example 2(c)] in dimethylformamide (25 ml) was treated with [O-(7-azabenzotriazol-1-yl)-1,1,3,3,-tetramethyluronium hexafluorophosphate (0.80 g) and diisopropylethylamine (0.75 ml). After stirring at room temperature for 2 hours the reaction mixture was treated with water (100 ml) then extracted three times with ethyl acetate. The combined organic extracts were washed with hydrochloric acid (1M), then with brine, then dried over magnesium sulphate and then evaporated. The residual oil was subjected to flash chromatography on silica eluting with a mixture of dichloromethane and methanol (25:1, v/v) to give 3-{[({[3-methoxy-4-(3-o-tolylureido)phenyl]-acetyl}-N-methylamino)-acetyl]-[3-(2-oxo-pyrrolidin-1-yl)-prop-1-yl]-amino}-propionic acid ethyl ester as a colourless oil (0.76 g). The ester was dissolved in tetrahydrofuran (50 ml) and then treated with lithium hydroxide hydrate (0.065 g) in water (10 ml). After stirring at room temperature for 2 hours the mixture was concentrated to remove the tetrahydrofuran. The residual aqueous residue was washed with ethyl acetate then acidified by addition of hydrochloric acid (1M) and then extracted three times with dichloromethane. The combined organic extracts were washed with brine, then dried over magnesium sulphate and then evaporated to give 3-{[({[3-methoxy-4-(3-o-tolylureido)phenyl]-acetyl}-N-methylamino)-acetyl]-[3-(2-oxo-pyrrolidin-1-yl)-prop-1-yl]-amino}-propionic acid as a white solid (0.58 g, Compound A), m.p.73-76° C. [Elemental analysis:- C,60.69; H,6.85; N,11.79% Calculated for C30H39N5O7.0.67H2O:- C,60.69; H,6.69; N,11.58%]. MS: 580 [MH]−. HPLC: RT=9.72 minutes (gradient elution using a mixture of acetonitrile and water 1:4 to 4:1).

Workup

  1. concentrationwas concentrated
  2. customto remove the tetrahydrofuran
  3. washThe residual aqueous residue was washed with ethyl acetate
  4. additionthen acidified by addition of hydrochloric acid (1M)
  5. extractionextracted three times with dichloromethane
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over magnesium sulphate
  8. customevaporated

Sources & evidence

ORD record
ord-f943cdc2431f44239270fa3362c8c49c
Source dataset
uspto-grants-2002_03
Patent number
US06352977B1

Reaction notes

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