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

HRID 2364744Notes

Reaction equation

HRID 2364744 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]([OH:28])=O)=[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.[CH:64]1([CH2:67][N:68]2[CH2:73][CH2:72][N:71]([CH2:74][C@@H:75]([O:78][CH3:79])[CH2:76][NH2:77])[CH2:70][CH2:69]2)[CH2:66][CH2:65]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:77][CH2:76][C@H:75]([O:78][CH3:79])[CH2:74][N:71]5[CH2:70][CH2:69][N:68]([CH2:67][CH:64]6[CH2:65][CH2:66]6)[CH2:73][CH2:72]5)=[O:28])=[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

7

Reactant 5

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 681074757-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acidHCID 68107823(2S)-3-[4-(cyclopropylmethyl)piperazin-1-yl]-2-methoxy-propan-1-amine

Product 1

HCID 510365847-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-[(2S)-3-[4-(cyclopropylmethyl)piperazin-1-yl]-2-methoxy-propyl]-2,3-dihydrobenzofuran-4-carboxamideYield 47.6%

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 (115 mg, 0.26 mmol) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetra methyluronium tetrafluoroborate (85 mg, 0.26 mmol) were dissolved in 30 mL of anhydrous dichloromethane followed by the addition of diisopropylethylamine (0.1 mL, 0.58 mmol) and the crude compound (2S)-3-[4-(cyclopropylmethyl)piperazin-1-yl]-2-methoxy-propan-1-amine 35d (60 mg, 0.26 mmol) successively. The reaction solution was stirred for 2 hours. The resulting solution was added with 30 mL of saturated sodium carbonate solution and extracted with dichloromethane (20 mL×3). The combined organic phase was washed with saturated sodium chloride solution (20 mL), 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-[(2S)-3-[4-(cyclopropylmethyl)piperazin-1-yl]-2-methoxy-propyl]-2,3-dihydrobenzofuran-4-carboxamide 35 (80 mg, yield: 47.0%) as a white solid.

Workup

  1. extractionextracted with dichloromethane (20 mL×3)
  2. washThe combined organic phase was washed with saturated sodium chloride solution (20 mL)
  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-ac0cc75019ba4b71b4b0f923da058b36
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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