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

HRID 2364698Notes

Reaction equation

HRID 2364698 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.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[CH2:64]([N:71]1[CH2:76][CH2:75][O:74][C@H:73]([CH2:77][NH2:78])[CH2:72]1)[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[CH2:64]([N:71]1[CH2:76][CH2:75][O:74][C@H:73]([CH2:77][NH:78][C:26]([C:20]2[CH:19]=[CH:18][C:17]([NH:16][C:13]3[N:12]=[CH:11][C:10]4[N:9]([CH3:29])[C:8](=[O:30])[C@@H:7]([CH2:31][CH3:32])[N:6]([CH:1]5[CH2:5][CH2:4][CH2:3][CH2:2]5)[C:15]=4[N:14]=3)=[C:25]3[O:24][CH2:23][CH2:22][C:21]=23)=[O:27])[CH2:72]1)[C:65]1[CH:66]=[CH:67][CH:68]=[CH:69][CH:70]=1

Participants

7

Reactant 5

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 6932056(2R)-4-(Phenylmethyl)-2-morpholinemethanamineHCID 681074757-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid

Product 1

HCID 68108134N-[[(2R)-4-benzylmorpholin-2-yl]methyl]-7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxamideYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

7-[[(7R)-8-Cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid 1q (276 mg, 0.63 mmol) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetra methyluronium tetrafluoroborate (202 mg, 0.63 mmol) were dissolved in 20 mL of anhydrous dichloromethane, added with diisopropylethylamine (0.2 mL, 1.4 mmol), [(2R)-4-benzylmorpholin-2-yl]methanamine 15a (130 mg, 0.63 mmol) successively with stirring. The reaction solution was stirred for 3 hours. The resulting solution was added with 10 mL saturated sodium carbonate solution and 10 mL of dichloromethane successively, and seperated. The organic phase was washed with sodium carbonate solution (50 mL×2), water (50 mL) and saturated sodium chloride solution (50 mL) successively, then dried over anhydrous sodium 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 N-[[(2R)-4-benzylmorpholin-2-yl]methyl]-7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxamide 15b (370 mg, yield: 94.0%) as a white solid.

Workup

  1. stirringThe reaction solution was stirred for 3 hours
  2. customseperated
  3. washThe organic phase was washed with sodium carbonate solution (50 mL×2), water (50 mL) and saturated sodium chloride solution (50 mL) successively
  4. dry with materialdried over anhydrous sodium 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-4c4ba74af02b49149e0a20f2e6d2560a
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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