Potassium Hydroxide → {5-[hydroxy-(7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methyl]-pyridin-2-yl}-(6-methoxy-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester

HRID 1775188Notes

Reaction equation

HRID 1775188 reaction equation
[N:1]1[C:6]2[NH:7][CH:8]=[CH:9][C:5]=2[CH:4]=[N:3][CH:2]=1.[C:10]([O:14][C:15](=[O:34])[N:16]([C:26]1[CH:31]=[CH:30][C:29]([CH:32]=[O:33])=[CH:28][N:27]=1)[CH2:17][C:18]1[CH:19]=[N:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=1)([CH3:13])([CH3:12])[CH3:11].[OH-].[K+].C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.CO>[C:10]([O:14][C:15](=[O:34])[N:16]([C:26]1[CH:31]=[CH:30][C:29]([CH:32]([OH:33])[C:9]2[C:5]3[CH:4]=[N:3][CH:2]=[N:1][C:6]=3[NH:7][CH:8]=2)=[CH:28][N:27]=1)[CH2:17][C:18]1[CH:19]=[N:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=1)([CH3:13])([CH3:11])[CH3:12]

Participants

7

Reactant 4

HCID 14797Potassium HydroxideHCID 2615917H-Pyrrolo(2,3-d)pyrimidineHCID 516892Sodium BicarbonateHCID 57619225(5-Formyl-pyridin-2-yl)-(6-methoxy-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester

Product 1

HCID 57963192{5-[hydroxy-(7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methyl]-pyridin-2-yl}-(6-methoxy-pyridin-3-ylmethyl)-carbamic acid tert-butyl esterYield 21.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

7H-Pyrrolo[2,3-d]pyrimidine (6, 0.450 g, 3.78 mmol), (5-formyl-pyridin-2-yl)-(6-methoxy-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester (71, 1.43 g, 4.16 mmol), potassium hydroxide (0.689 g, 12.3 mmol) and 6.6 mL methanol were combined in a reaction vessel. The reaction mixture was allowed to stir at room temperature for 36 hours, then concentrated under vacuum to provide a thick brown slurry, which was combined with ethyl acetate and aqueous saturated sodium bicarbonate. The organic layer was dried with sodium sulfate, filtered and the filtrate adsorbed onto silica. This was purified by silica gel column chromatography, eluting with a gradient of 1-10% methanol in dichloromethane over 30 minutes. Appropriate fractions were combined and the solvents removed under vacuum to provide the desired compound (72, 380 mg). 1H NMR was consistent with the compound structure.

Workup

  1. concentrationconcentrated under vacuum
  2. customto provide a thick brown slurry, which
  3. dry with materialThe organic layer was dried with sodium sulfate
  4. filtrationfiltered
  5. customThis was purified by silica gel column chromatography
  6. washeluting with a gradient of 1-10% methanol in dichloromethane over 30 minutes
  7. customthe solvents removed under vacuum

Sources & evidence

ORD record
ord-e64d870d3e5e469aaa13ee5a3924748c
Source dataset
uspto-grants-2016_02
Patent number
US09260437B2

Reaction notes

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