Hydrochloric Acid → 2-{2-[(Furan-2-carbonyl)-amino]-pyrimidin-4-yl}-1-methyl-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester

HRID 869331Notes

Reaction equation

HRID 869331 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[NH:14][C:15]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH2:23])[N:18]=3)=[CH:16][C:10]=2[C:9]1=[O:24])=[O:7])([CH3:4])([CH3:3])[CH3:2].[O:25]1[CH:29]=[CH:28][CH:27]=[C:26]1[C:30](Cl)=[O:31].[OH-].[Na+].Cl.[CH2:36](Cl)Cl>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[N:14]([CH3:36])[C:15]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:30]([C:26]4[O:25][CH:29]=[CH:28][CH:27]=4)=[O:31])[N:18]=3)=[CH:16][C:10]=2[C:9]1=[O:24])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 682422-Furancarbonyl chlorideHCID 247769152-(2-Amino-pyrimidin-4-yl)-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester

Product 1

HCID 672855172-{2-[(Furan-2-carbonyl)-amino]-pyrimidin-4-yl}-1-methyl-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl esterYield 24%

Procedure

To a solution of 2-(2-amino-pyrimidin-4-yl)-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]-pyridine-5-carboxylic acid tert-butyl ester (prepared as described in Example 9) (0.255 mmol, 1 eq) in 2.5 mL of dry DCM and TEA (1.617 mmol, 6.3 eq) under argon atmosphere, 2-furane-carbonylchloride (0.803 mmol, 3.15 eq) was added at room temperature within 10 minutes. After stirring for 3 h at room temperature, the solvent was evaporated, the crude dissolved in 2 ml of MeOH and treated with 2.1 equivalents of NaOH 1N. The mixture was stirred for 2 h at room temperature until HPLC revealed conversion of starting diacylated product into the monoacylated; finally stoichiometric amount of HCl 2N was added. The methanol was evaporated under vacuum and the crude was washed with water and extracted twice with CH2Cl2, dried over Na2SO4 and evaporated to dryness. The residue was then purified by flash column chromatography (98:2 CH2Cl2:MeOH) affording 2-{2-[(furan-2-carbonyl)-amino]-pyrimidin-4-yl}-1-methyl-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester as a white solid in 24% yield.

Workup

  1. customthe solvent was evaporated
  2. dissolutionthe crude dissolved in 2 ml of MeOH
  3. stirringThe mixture was stirred for 2 h at room temperature until HPLC
  4. customThe methanol was evaporated under vacuum
  5. washthe crude was washed with water
  6. extractionextracted twice with CH2Cl2
  7. dry with materialdried over Na2SO4
  8. customevaporated to dryness
  9. customThe residue was then purified by flash column chromatography (98:2 CH2Cl2:MeOH)

Sources & evidence

ORD record
ord-689150bba94d439e8905063d73aa1f3b
Source dataset
uspto-grants-2015_03
Patent number
US08969366B2

Reaction notes

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