Methanol → HCID 59038381, compound

HRID 1058449Notes

Reaction equation

HRID 1058449 reaction equation
[OH-].[Na+].C[O:4][C:5](=[O:39])/[C:6](/[NH:18][C:19](=[O:38])[C:20]1[CH:25]=[CH:24][C:23]([C:26]([NH:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([OH:36])[CH:31]=2)=[O:27])=[CH:22][C:21]=1[Cl:37])=[CH:7]/[C:8]1[S:12][C:11]([NH2:13])=[N:10][C:9]=1[C:14]([F:17])([F:16])[F:15].[CH3:40]O>>[NH2:13][C:11]1[S:12][C:8](/[CH:7]=[C:6](\[NH:18][C:19](=[O:38])[C:20]2[CH:25]=[CH:24][C:23]([C:26]([NH:28][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([OH:36])[CH:31]=3)=[O:27])=[CH:22][C:21]=2[Cl:37])/[C:5]([OH:39])=[O:4])=[C:9]([C:14]([F:15])([F:16])[F:17])[N:10]=1.[Cl:37][C:21]1[CH:22]=[C:23]([C:26]([NH:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([OH:36])[CH:31]=2)=[O:27])[CH:24]=[CH:25][C:20]=1[C:19]([NH:18]/[C:6](=[CH:7]\[C:8]1[S:12][C:11]([NH:13][CH3:40])=[N:10][C:9]=1[C:14]([F:17])([F:15])[F:16])/[C:5]([OH:4])=[O:39])=[O:38]

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 23560792HCID 23560792, compound

Product 2

HCID 59038381HCID 59038381, compoundHCID 59038428HCID 59038428, compound

Procedure

An aqueous 3N solution of sodium hydroxide (0.5 mL, 1.5 mmol) was added to a solution of (Z)-3-(2-amino-4-trifluoromethylthiazol-5-yl)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]propenoic acid methyl ester (Example 234; 90 mg, 0.16 mmol) in methanol (0.5 mL). The solution was stirred at room temperature for 16 h and then at 50° C. for 2 h. The reaction mixture was evaporated to dryness and the residue was dissolved in water (2 mL). 1N Hydrochloric acid solution (1.5 mL) was added and the resulting yellow solid was filtered off and washed well with water. The mixture of crude acids was purified by reverse phase HPLC and lyophilized to give (Z)-3-(2-amino-4-trifluoromethylthiazol-5-yl)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]propenoic acid (15 mg) and (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-(2-methylamino-4-trifluoromethylthiazol-5-yl)propenoic acid (15 mg).

Workup

  1. waitat 50° C. for 2 h
  2. customThe reaction mixture was evaporated to dryness
  3. dissolutionthe residue was dissolved in water (2 mL)
  4. addition1N Hydrochloric acid solution (1.5 mL) was added
  5. filtrationthe resulting yellow solid was filtered off
  6. washwashed well with water
  7. additionThe mixture of crude acids
  8. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-0c08ede2ef2c463788a3287c6e9d6448
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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