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

HRID 2364745Notes

Reaction equation

HRID 2364745 reaction equation
[CH2:1]([C@H:3]1[N:12]([CH:13]([CH3:15])[CH3:14])[C:11]2[N:10]=[C:9]([NH:16][C:17]3[CH:18]=[CH:19][C:20]([C:26]([OH:28])=O)=[C:21]4[C:25]=3[O:24][CH2:23][CH2:22]4)[N:8]=[CH:7][C:6]=2[N:5]([CH3:29])[C:4]1=[O:30])[CH3:2].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:62]1([CH2:65][N:66]2[CH2:71][CH2:70][N:69]([CH2:72][C@@H:73]([O:76][CH3:77])[CH2:74][NH2:75])[CH2:68][CH2:67]2)[CH2:64][CH2:63]1.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[CH:62]1([CH2:65][N:66]2[CH2:67][CH2:68][N:69]([CH2:72][C@@H:73]([O:76][CH3:77])[CH2:74][NH:75][C:26]([C:20]3[CH:19]=[CH:18][C:17]([NH:16][C:9]4[N:8]=[CH:7][C:6]5[N:5]([CH3:29])[C:4](=[O:30])[C@@H:3]([CH2:1][CH3:2])[N:12]([CH:13]([CH3:15])[CH3:14])[C:11]=5[N:10]=4)=[C:25]4[O:24][CH2:23][CH2:22][C:21]=34)=[O:28])[CH2:70][CH2:71]2)[CH2:63][CH2:64]1

Participants

7

Reactant 5

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 68107823(2S)-3-[4-(cyclopropylmethyl)piperazin-1-yl]-2-methoxy-propan-1-amineHCID 681080517-[[(7R)-7-ethyl-8-isopropyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid

Product 1

HCID 51036585N-[(2S)-3-[4-(cyclopropylmethyl)piperazin-1-yl]-2-methoxy-propyl]-7-[[(7R)-7-ethyl-8-isopropyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxamideYield 38%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

7-[[(7R)-7-Ethyl-8-isopropyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid 22f (70 mg, 0.17 mmol) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetra methyluronium tetrafluoroborate (55 mg, 0.17 mmol) were dissolved in mL of anhydrous dichloromethane followed by the addition of diisopropylethylamine (0.1 mL, 0.58 mmol) and (2S)-3-[4-(cyclopropylmethyl)piperazin-1-yl]-2-methoxy-propan-1-amine 35d (39 mg, 0.17 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 (30 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 N-[(2S)-3-[4-(cyclopropylmethyl)piperazin-1-yl]-2-methoxy-propyl]-7-[[(7R)-7-ethyl-8-isopropyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxamide 36 (40 mg, yield: 38.0%) as a white solid.

Workup

  1. extractionextracted with dichloromethane (20 mL×3)
  2. washThe combined organic phase was washed with saturated sodium chloride solution (30 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-1a29f3c42a934025abc6a1194420f77e
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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