Sodium Carbonate → 7-[[(7S)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-(1-methyl-4-piperidyl)-2,3-dihydrobenzofuran-4-carboxamide

HRID 2364759Notes

Reaction equation

HRID 2364759 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](O)=[O:27])=[C:21]5[C:25]=4[O:24][CH2:23][CH2:22]5)[N:12]=[CH:11][C:10]=3[N:9]([CH3:29])[C:8](=[O:30])[C@@H:7]2[CH2:31][CH3:32])[CH2:5][CH2:4][CH2:3][CH2:2]1.F[B-](F)(F)F.[N:38]1(OC(N(C)C)=[N+](C)C)[C:42]2[CH:43]=[CH:44]C=[CH:46][C:41]=2N=N1.[CH:55]([N:58](C(C)C)CC)(C)C.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[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:38][CH:42]5[CH2:41][CH2:46][N:58]([CH3:55])[CH2:44][CH2:43]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]([CH3:29])[C:8](=[O:30])[C@@H:7]2[CH2:31][CH3:32])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 681076557-[[(7S)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid

Product 1

HCID 510367887-[[(7S)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-(1-methyl-4-piperidyl)-2,3-dihydrobenzofuran-4-carboxamideYield 66.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

7-[[(7S)-8-Cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid 41g (150 mg, 0.34 mmol) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetra methyluronium tetrafluoroborate (111 mg, 0.34 mmol) were dissolved in 30 mL of dichloromethane followed by the addition of diisopropylethylamine (0.13 mL, 0.76 mmol), stirred for 10 minute, then added with 1-methyl-piperidyl-4-yl-amine (40 mg, 0.34 mmol), stirred at room temperature for 1 hour. The reaction mixture was added with 20 mL of saturated sodium carbonate solution and extracted with dichloromethane (100 mL×2). The combined organic phase was washed with water (20 mL) and saturated sodium chloride solution (20 mL) successively, 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 with elution system A to obtain the title compound 7-[[(7S)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-(1-methyl-4-piperidyl)-2,3-dihydrobenzofuran-4-carboxamide 41 (120 mg, yield: 65.0%) as a white solid.

Workup

  1. stirringstirred at room temperature for 1 hour
  2. extractionextracted with dichloromethane (100 mL×2)
  3. washThe combined organic phase was washed with water (20 mL) and saturated sodium chloride solution (20 mL) successively
  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 with elution system

Sources & evidence

ORD record
ord-82656d187fec48dc918d66a4bfcf9dbc
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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