Ammonia → HCID 178455834, compound

HRID 2364768Notes

Reaction equation

HRID 2364768 reaction equation
[CH:1]1([CH2:4][N:5]2[CH2:10][CH2:9][N:8]([C@@H:11]3[CH2:16][CH2:15][C@H:14]([NH2:17])[CH2:13][CH2:12]3)[CH2:7][CH2:6]2)[CH2:3][CH2:2]1.[CH:18]([N:21]1[C:30]2[N:29]=[C:28]([NH:31][C:32]3[CH:33]=[CH:34][C:35]([C:41](O)=[O:42])=[C:36]4[C:40]=3[O:39][CH2:38][CH2:37]4)[N:27]=[CH:26][C:25]=2[N:24]([CH3:44])[C:23](=[O:45])[C@@H:22]1[CH2:46][CH3:47])([CH3:20])[CH3:19].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.N>ClCCl>[CH:1]1([CH2:4][N:5]2[CH2:10][CH2:9][N:8]([C@@H:11]3[CH2:16][CH2:15][C@H:14]([NH:17][C:41]([C:35]4[CH:34]=[CH:33][C:32]([NH:31][C:28]5[N:27]=[CH:26][C:25]6[N:24]([CH3:44])[C:23](=[O:45])[C@H:22]([CH2:46][CH3:47])[N:21]([CH:18]([CH3:19])[CH3:20])[C:30]=6[N:29]=5)=[C:40]5[O:39][CH2:38][CH2:37][C:36]=45)=[O:42])[CH2:13][CH2:12]3)[CH2:7][CH2:6]2)[CH2:2][CH2:3]1

Participants

7

Reactant 5

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 510369997-[[(7S)-8-isopropyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acidHCID 178511578HCID 178511578, compound

Product 1

HCID 178455834HCID 178455834, compoundYield 74.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(cis)-4-[4-(Cyclopropylmethyl)piperazin-1-yl]cyclohexanamine 12e (577 mg, 2.43 mmol), the crude compound 7-[[(7S)-8-isopropyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid 43e (1 g, 2.43 mmol), O-(benzotriazol-1-yl)-N,N,N′,N′-tetra methyluronium tetrafluoroborate (780 mg, 2.43 mmol) and diisopropylethylamine (690 mg, 5.35 mmol) were dissolved in 60 mL of dichloromethane. The reaction solution was stirred for 2 hours. The resulting mixture was added with 50 mL of aqueous ammonia and extracted with dichloromethane (50 mL×3). The combined organic phase was washed with saturated brine (50 mL×3), then dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography with elution system A to obtain the title compound N-[(cis)-4-[4-(cyclopropylmethyl)piperazin-1-yl]cyclohexyl]-7-[[(7S)-7-ethyl-8-isopropyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxamide 43 (1.12 g, yield: 74.6%) as a white solid.

Workup

  1. extractionextracted with dichloromethane (50 mL×3)
  2. washThe combined organic phase was washed with saturated brine (50 mL×3)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography with elution system

Sources & evidence

ORD record
ord-9f5306f96728477dbb971fce3e9350b9
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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