Sodium Carbonate → HCID 178455833, compound

HRID 2364746Notes

Reaction equation

HRID 2364746 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]([C@H:72]3[CH2:77][CH2:76][C@H:75]([NH2:78])[CH2:74][CH2:73]3)[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[CH2:71][CH2:70][N:69]([C@H:72]3[CH2:77][CH2:76][C@H:75]([NH:78][C:26]([C:20]4[CH:19]=[CH:18][C:17]([NH:16][C:9]5[N:8]=[CH:7][C:6]6[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]=6[N:10]=5)=[C:25]5[O:24][CH2:23][CH2:22][C:21]=45)=[O:28])[CH2:74][CH2:73]3)[CH2:68][CH2:67]2)[CH2:63][CH2:64]1

Participants

7

Reactant 5

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 681080517-[[(7R)-7-ethyl-8-isopropyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acidHCID 178511579HCID 178511579, compound

Product 1

HCID 178455833HCID 178455833, compoundYield 23.3%

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 15 mL of anhydrous dichloromethane followed by the addition of diisopropylethylamine (0.1 mL, 0.37 mmol) and (trans) 4-[4-(cyclopropylmethyl)piperazin-1-yl]cyclohexanamine 16b (40 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 (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 N-[(trans)-4-[4-(cyclopropylmethyl)piperazin-1-yl]cyclohexyl]-7-[[(7R)-7-ethyl-8-isopropyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxamide 37 (25 mg, yield: 23.0%) 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-f92dec100b554ef1978ad755ceef5971
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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