Hydrochloric Acid → 2-(1-(Cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylic acid

HRID 2275026Notes

Reaction equation

HRID 2275026 reaction equation
[CH:1]1([CH2:4][N:5]2[C:9]3=[N:10][CH:11]=[CH:12][CH:13]=[C:8]3[CH:7]=[C:6]2[C:14]2[N:18]([CH3:19])[C:17]3[C:20]([O:28][CH3:29])=[CH:21][C:22]([C:24]([O:26]C)=[O:25])=[CH:23][C:16]=3[N:15]=2)[CH2:3][CH2:2]1.O.[OH-].[Li+].Cl>O1CCCC1.O>[CH:1]1([CH2:4][N:5]2[C:9]3=[N:10][CH:11]=[CH:12][CH:13]=[C:8]3[CH:7]=[C:6]2[C:14]2[N:18]([CH3:19])[C:17]3[C:20]([O:28][CH3:29])=[CH:21][C:22]([C:24]([OH:26])=[O:25])=[CH:23][C:16]=3[N:15]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 86340160Methyl 2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate

Product 1

HCID 863401542-(1-(Cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylic acidYield 41.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl 2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (260 mg, 0.666 mmol) was dissolved in a 1:1 ratio of tetrahydrofuran (THF) (3.2 mL) and water (3.2 mL). To this was added lithium hydroxide monohydrate (140 mg, 3.33 mmol) and the reaction stirred at rt for 16 h. The reaction mixture was acidified by the addition of 2M HCl(aq) (20 mL) and the organics extracted into 10% MeOH/DCM (20 mL). The aqueous layer was washed with 10% MeOH/DCM (2×20 mL) and the combined organics dried (Na2SO4) and concentrated in vacuo to afford a yellow oil which solidified on standing (44 mg). Due to the poor recovery it was assumed the remainder of the product remained in the aqueous layer. The aqueous layer was further extracted with EtOAc (20 mL), DCM (2×20 mL) and 10% MeOH/DCM (8×10 mL). The combined organics were dried (Na2SO4) and concentrated in vacuo. Both crude products were combined together to form 2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylic acid (105 mg, 0.279 mmol, 41.9% yield).

Workup

  1. extractionthe organics extracted into 10% MeOH/DCM (20 mL)
  2. washThe aqueous layer was washed with 10% MeOH/DCM (2×20 mL)
  3. dry with materialthe combined organics dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customto afford a yellow oil which
  6. extractionThe aqueous layer was further extracted with EtOAc (20 mL), DCM (2×20 mL) and 10% MeOH/DCM (8×10 mL)
  7. dry with materialThe combined organics were dried (Na2SO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-46f259c4a7c940708ab46b4d8c3163bd
Source dataset
uspto-grants-2015_09
Patent number
US09127003B2

Reaction notes

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