Methanol → HCID 68686684, compound

HRID 2244233Notes

Reaction equation

HRID 2244233 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][NH:8][C:9]([C:11]2[N:20]3[C:14]([CH2:15][N:16]([C:25]([C:27]4[CH:32]=[CH:31][C:30]([C:33]5[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=5[CH2:39][C:40]([O:42]C)=[O:41])=[CH:29][CH:28]=4)=[O:26])[C:17]4[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=4[CH2:19]3)=[CH:13][CH:12]=2)=[O:10])[CH:2]=1.CO.O.[OH-].[Li+]>O>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][NH:8][C:9]([C:11]2[N:20]3[C:14]([CH2:15][N:16]([C:25]([C:27]4[CH:32]=[CH:31][C:30]([C:33]5[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=5[CH2:39][C:40]([OH:42])=[O:41])=[CH:29][CH:28]=4)=[O:26])[C:17]4[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=4[CH2:19]3)=[CH:13][CH:12]=2)=[O:10])[CH:2]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 168937Lithium hydroxide, monohydrateHCID 15952973HCID 15952973, compound

Product 1

HCID 68686684HCID 68686684, compoundYield 66.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of methyl (4′-{[3-{[(pyridin-3-ylmethyl)amino]carbonyl}-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-yl]carbonyl}-1,1′-biphenyl-2-yl)acetate of Example 32 (0.585 g, 1.03 mmol) in 2:1 v/v methanol:water (12 mL) was added lithium hydroxide monohydrate (87 mg, 2.07 mmol) and the mixture heated to reflux for 90 minutes. The cooled reaction mixture was concentrated in vacuo to remove methanol and then diluted with water (10 mL). The aqueous phase was washed with ethyl acetate (2×10 mL) then slowly added to a mixture of 1 M aqueous hydrochloric acid (2.2 mL) in water (20 mL) and the resulting suspension cooled to 0° C. for 1 hour. Filtration afforded the title compound (0.381 g, 66%) as a tan solid.

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 90 minutes
  3. customThe cooled reaction mixture
  4. concentrationwas concentrated in vacuo
  5. customto remove methanol
  6. additiondiluted with water (10 mL)
  7. washThe aqueous phase was washed with ethyl acetate (2×10 mL)
  8. additionthen slowly added to a mixture of 1 M aqueous hydrochloric acid (2.2 mL) in water (20 mL)
  9. filtrationFiltration

Sources & evidence

ORD record
ord-5ef90626292648b799c5d993d806f961
Source dataset
uspto-grants-2010_03
Patent number
US07678787B2

Reaction notes

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