Formaldehyde → 7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-[(4-methylmorpholin-2-yl)methyl]-2,3-dihydrobenzofuran-4-carboxamide

HRID 2364674Notes

Reaction equation

HRID 2364674 reaction equation
[CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([NH:16][C:17]4[CH:18]=[CH:19][C:20]([C:26]([NH:28][CH2:29][CH:30]5[O:35][CH2:34][CH2:33][NH:32][CH2:31]5)=[O:27])=[C:21]5[C:25]=4[O:24][CH2:23][CH2:22]5)[N:12]=[CH:11][C:10]=3[N:9]([CH3:36])[C:8](=[O:37])[C@H:7]2[CH2:38][CH3:39])[CH2:5][CH2:4][CH2:3][CH2:2]1.C=O.[C:42](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(#N)C.O>[CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([NH:16][C:17]4[CH:18]=[CH:19][C:20]([C:26]([NH:28][CH2:29][CH:30]5[O:35][CH2:34][CH2:33][N:32]([CH3:42])[CH2:31]5)=[O:27])=[C:21]5[C:25]=4[O:24][CH2:23][CH2:22]5)[N:12]=[CH:11][C:10]=3[N:9]([CH3:36])[C:8](=[O:37])[C@H:7]2[CH2:38][CH3:39])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 681078727-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-(morpholin-2-ylmethyl)-2,3-dihydrobenzofuran-4-carboxamide

Product 1

HCID 510382707-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-[(4-methylmorpholin-2-yl)methyl]-2,3-dihydrobenzofuran-4-carboxamideYield 38%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

The crude compound 7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-(morpholin-2-ylmethyl)-2,3-dihydrobenzofuran-4-carboxamide 2f (163 mg, 0.30 mmol) was dissolved in 60 mL of the mixture solvent of acetonitrile and water (V/V=1:1) in an ice-water bath, the reaction solution was cooled down to 0° C. followed by the addition of formaldehyde (18 mg, 0.60 mmol) and sodium triacetoxyborohydride (191 mg, 0.90 mmol), warmed up slowly to room temperature and stirred for 2 hours. The resulting mixture was added dropwise with saturated sodium bicarbonate solution to adjust pH to 9 to 10, extracted with dichloromethane (50 mL×3). The combined organic phase was washed with saturated sodium chloride solution (50 mL×3), then dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound 7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-[(4-methylmorpholin-2-yl)methyl]-2,3-dihydrobenzofuran-4-carboxamide 2 (62 mg, yield: 38.0%) as a white solid.

Workup

  1. temperaturewarmed up slowly to room temperature
  2. extractionextracted with dichloromethane (50 mL×3)
  3. washThe combined organic phase was washed with saturated sodium chloride solution (50 mL×3)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-0884bd2cc1cc49b29fa8850702eaa419
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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