Hydrochloric Acid → methyl 3-(5-(4,6-dichloro-N-(2-hydroxyethyl)pyrimidine-5-carboxamido)pyridin-2-yloxy)-2,2-dimethylpropanoate

HRID 473969Notes

Reaction equation

HRID 473969 reaction equation
Cl.[Si]([O:9][CH2:10][CH2:11][N:12]([C:23]1[CH:24]=[CH:25][C:26]([O:29][CH2:30][C:31]([CH3:37])([CH3:36])[C:32]([O:34][CH3:35])=[O:33])=[N:27][CH:28]=1)[C:13]([C:15]1[C:16]([Cl:22])=[N:17][CH:18]=[N:19][C:20]=1[Cl:21])=[O:14])(C(C)(C)C)(C)C>CO>[Cl:22][C:16]1[C:15]([C:13]([N:12]([C:23]2[CH:24]=[CH:25][C:26]([O:29][CH2:30][C:31]([CH3:36])([CH3:37])[C:32]([O:34][CH3:35])=[O:33])=[N:27][CH:28]=2)[CH2:11][CH2:10][OH:9])=[O:14])=[C:20]([Cl:21])[N:19]=[CH:18][N:17]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 58577890methyl 3-(5-(N-(2-(tert-butyldimethylsilyloxy)ethyl)-4,6-dichloropyrimidine-5-carboxamido)pyridin-2-yloxy)-2,2-dimethylpropanoate

Product 1

HCID 86660661methyl 3-(5-(4,6-dichloro-N-(2-hydroxyethyl)pyrimidine-5-carboxamido)pyridin-2-yloxy)-2,2-dimethylpropanoate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A concentrated aqueous solution of hydrogen chloride (34-37.5%, 0.1 mL) was added at room temperature to a solution of methyl 3-(5-(N-(2-(tert-butyldimethylsilyloxy)ethyl)-4,6-dichloropyrimidine-5-carboxamido)pyridin-2-yloxy)-2,2-dimethylpropanoate B-19 (139.4 mg, 0.25 mmol) in methanol (2.0 mL). The reaction mixture was stirred for 30 mins at room temperature and concentrated to dryness under reduced pressure. The residue was dissolved in ethyl acetate, successively washed with a saturated aqueous solution of sodium bicarbonate and brine, dried over anhydrous sodium sulfate, filtered and concentrated to dryness under reduced pressure to give crude intermediate methyl 3-(5-(4,6-dichloro-N-(2-hydroxyethyl)pyrimidine-5-carboxamido)pyridin-2-yloxy)-2,2-dimethylpropanoate (MS (ESI) [M+1]+ 444), which was then dissolved in acetonitrile (2.0 mL). Triethylamine (0.14 mL, 1.0 mmol) was then added at room temperature, and the reaction mixture was heated at 100° C. for 3 h then concentrated to dryness under reduced pressure. The residue was dissolved in ethyl acetate, successively washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated to dryness under reduced pressure to give methyl 3-(5-(4-chloro-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)pyridin-2-yloxy)-2,2-dimethylpropanoate B-20. This material was used for the next step without purification. MS (ESI) [M+1]+ 407.

Workup

  1. concentrationconcentrated to dryness under reduced pressure
  2. dissolutionThe residue was dissolved in ethyl acetate
  3. washsuccessively washed with a saturated aqueous solution of sodium bicarbonate and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-94e012df640347b1b543de7b32dd319b
Source dataset
uspto-grants-2014_01
Patent number
US08637507B2

Reaction notes

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