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

HRID 2364723Notes

Reaction equation

HRID 2364723 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.[NH2:64][CH2:65][C@@H:66]([OH:75])[CH2:67][N:68]1[CH2:73][CH2:72][N:71]([CH3:74])[CH2:70][CH2:69]1.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:64][CH2:65][C@@H:66]([OH:75])[CH2:67][N:68]5[CH2:69][CH2:70][N:71]([CH3:74])[CH2:72][CH2:73]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])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 5

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 28279114(2R)-1-amino-3-(4-methylpiperazin-1-yl)propan-2-olHCID 681074757-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid

Product 1

HCID 510359697-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-[(2R)-2-hydroxy-3-(4-methylpiperazin-1-yl)propyl]-2,3-dihydrobenzofuran-4-carboxamideYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

7-[[(7R)-8-Cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid 1q (150 mg, 0.34 mmol) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetra methyluronium tetrafluoroborate (110 mg, 0.34 mmol) were dissolved in 30 mL of anhydrous dichloromethane, followed by the addition of diisopropylethylamine (0.1 mL, 0.75 mmol) and (2R)-1-amino-3-(4-methylpiperazin-1-yl)propan-2-ol 20e (59 mg, 0.34 mmol). The reaction solution was stirred for 3 hours. The resulting solution was added with 30 mL of saturated sodium carbonate solution and extracted with dichloromethane (50 mL×3). The combined organic phase was washed with saturated sodium carbonate solution (50 mL×3), 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 7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-[(2R)-2-hydroxy-3-(4-methylpiperazin-1-yl)propyl]-2,3-dihydrobenzofuran-4-carboxamide 25 (120 mg, yield: 60.0%) as a white solid.

Workup

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

Sources & evidence

ORD record
ord-a50e9122ab354ed6af7ffcbf731f328b
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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