Methanol → {5-[(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-methoxy-methyl]-pyridin-2-yl}-(6-methoxy-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester

HRID 510002Notes

Reaction equation

HRID 510002 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[C:11]([O:15][C:16](=[O:35])[N:17]([C:27]1[CH:32]=[CH:31][C:30]([CH:33]=[O:34])=[CH:29][N:28]=1)[CH2:18][C:19]1[CH:20]=[N:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=1)([CH3:14])([CH3:13])[CH3:12].[OH-].[K+].O.[CH3:39]O>>[C:11]([O:15][C:16](=[O:35])[N:17]([C:27]1[CH:32]=[CH:31][C:30]([CH:33]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([Br:1])[CH:3]=3)[NH:8][CH:9]=2)[O:34][CH3:39])=[CH:29][N:28]=1)[CH2:18][C:19]1[CH:20]=[N:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=1)([CH3:14])([CH3:12])[CH3:13]

Participants

6

Reactant 5

HCID 887MethanolHCID 962WaterHCID 14797Potassium HydroxideHCID 103079325-bromo-1H-pyrrolo[2,3-b]pyridineHCID 57619225(5-Formyl-pyridin-2-yl)-(6-methoxy-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester

Product 1

HCID 58259147{5-[(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-methoxy-methyl]-pyridin-2-yl}-(6-methoxy-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester

Procedure

To 5-bromo-1H-pyrrolo[2,3-b]pyridine (152, 0.622 g, 3.16 mmol) in 50.0 mL of methanol under nitrogen, (5-formyl-pyridin-2-yl)-(6-methoxy-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester (153, 1.05 g, 3.06 mmol) and potassium hydroxide (1.50 g, 26.7 mmol) were added and the reaction stirred at room temperature overnight. The reaction was poured into water, extracted with ethyl acetate, the organic layer dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluting with a gradient of 20-100% ethyl acetate in hexane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound (154, 0.35 g). {5-[(5-Bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-hydroxy-methyl]-pyridin-2-yl}-(6-methoxy-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester was also formed in this procedure and could be isolated and reacted similarly to the following step to form the desired product.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialthe organic layer dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationthe filtrate concentrated under vacuum
  5. customThe resulting material was purified by silica gel column chromatography
  6. washeluting with a gradient of 20-100% ethyl acetate in hexane
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-9925529599bc453e8c2a4cf8a850d488
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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