Ammonia → HCID 178455834, compound

HRID 2364770Notes

Reaction equation

HRID 2364770 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.[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

8

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 178511579HCID 178511579, compound

Product 2

HCID 178455834HCID 178455834, compoundYield 77.1%HCID 178455835HCID 178455835, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(trans)-4-[4-(Cyclopropylmethyl)piperazin-1-yl]cyclohexanamine 16b (350 mg, 1.48 mmol), 7-[[(7S)-7-ethyl-8-isopropyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid 43e (607 mg, 1.48 mmol), O-(benzotriazol-1-yl)-N,N,N′,N′-tetra methyluronium tetrafluoroborate (475 mg, 1.48 mmol) and diisopropylethylamine (420 mg, 3.30 mmol) were dissolved in 40 mL of dichloromethane. The reaction solution was stirred for 2 hours. The resulting solution 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 45 (360 mg, yield: 38.0%) 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-d17bcc48c3bd4efdae1a34c1a133e701
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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