Diisopropylethylamine → 7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,2-dimethyl-N-(1-methyl-4-piperidyl)-3H-benzofuran-4-carboxamide

HRID 2364684Notes

Reaction equation

HRID 2364684 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:28]([OH:30])=O)=[C:21]5[C:25]=4[O:24][C:23]([CH3:27])([CH3:26])[CH2:22]5)[N:12]=[CH:11][C:10]=3[N:9]([CH3:31])[C:8](=[O:32])[C@H:7]2[CH2:33][CH3:34])[CH2:5][CH2:4][CH2:3][CH2:2]1.F[B-](F)(F)F.[N:40]1(OC(N(C)C)=[N+](C)C)[C:44]2[CH:45]=[CH:46]C=[CH:48][C:43]=2N=N1.[CH:57]([N:60](C(C)C)CC)(C)C.C(=O)(O)[O-].[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:28]([NH:40][CH:44]5[CH2:43][CH2:48][N:60]([CH3:57])[CH2:46][CH2:45]5)=[O:30])=[C:21]5[C:25]=4[O:24][C:23]([CH3:26])([CH3:27])[CH2:22]5)[N:12]=[CH:11][C:10]=3[N:9]([CH3:31])[C:8](=[O:32])[C@H:7]2[CH2:33][CH3:34])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 681074737-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,2-dimethyl-3H-benzofuran-4-carboxylic acid

Product 1

HCID 510382727-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,2-dimethyl-N-(1-methyl-4-piperidyl)-3H-benzofuran-4-carboxamideYield 70.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

7-[[(7R)-8-Cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,2-dimethyl-3H-benzofuran-4-carboxylic acid 4f (931 mg, 2 mmol) was dissolved in 50 mL of dichloromethane followed by the addition of 1-methyl-piperidyl-4-yl-amine (228 mg, 2 mmol), O-(benzotriazol-1-yl)-N,N,N′,N′-tetra methyluronium tetrafluoroborate (642 mg, 2 mmol) and diisopropylethylamine (775 mg, 6 mmol). The reaction solution was stirred for 1.5 hours. The resulting mixture was added with 50 mL of saturated sodium bicarbonate solution, extracted with dichloromethane (50 mL×3). The combined organic phase was washed with water (15 mL), saturated sodium chloride solution (15 mL) successively, dried over anhydrous magnesium sulfate. 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]-2,2-dimethyl-N-(1-methyl-4-piperidyl)-3H-benzofuran-4-carboxamide 4 (793 mg, yield: 70.8%) as a white solid.

Workup

  1. extractionextracted with dichloromethane (50 mL×3)
  2. washThe combined organic phase was washed with water (15 mL), saturated sodium chloride solution (15 mL) successively
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-feb48562357443aa91ce57ea12c68d37
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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