Triethylamine → N-[(3R,6S)-6-(2,3-Difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(8-oxo-8,9-dihydro-7H-purin-7-yl)piperidine-1-carboxamide

HRID 20166Notes

Reaction equation

HRID 20166 reaction equation
C(N(CC)CC)C.[NH2:8][C@@H:9]1[CH2:15][CH2:14][C@@H:13]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:17]=2[F:23])[CH2:12][N:11]([CH2:24][C:25]([F:28])([F:27])[F:26])[C:10]1=[O:29].Cl[C:31](OC1C=CC([N+]([O-])=O)=CC=1)=[O:32].Cl.[NH:44]1[CH2:49][CH2:48][CH:47]([N:50]2[C:58]3[C:53](=[N:54][CH:55]=[N:56][CH:57]=3)[NH:52][C:51]2=[O:59])[CH2:46][CH2:45]1>O1CCCC1>[F:23][C:17]1[C:18]([F:22])=[CH:19][CH:20]=[CH:21][C:16]=1[C@H:13]1[CH2:12][N:11]([CH2:24][C:25]([F:28])([F:26])[F:27])[C:10](=[O:29])[C@H:9]([NH:8][C:31]([N:44]2[CH2:49][CH2:48][CH:47]([N:50]3[C:58]4[C:53](=[N:54][CH:55]=[N:56][CH:57]=4)[NH:52][C:51]3=[O:59])[CH2:46][CH2:45]2)=[O:32])[CH2:15][CH2:14]1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 821294-Nitrophenyl chloroformateHCID 222931977-Piperidin-4-yl-7,9-dihydro-8H-purin-8-one hydrochlorideHCID 23653826(3R,6S)-3-Amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepan-2-one

Product 1

HCID 11169053N-[(3R,6S)-6-(2,3-Difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(8-oxo-8,9-dihydro-7H-purin-7-yl)piperidine-1-carboxamideYield 92.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (0.030 mL, 0.215 mmol) was added to a solution of (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepan-2-one (80 mg, 0.248 mmol) and 4-nitrophenyl chloroformate (44 mg, 0.218 mmol) in tetrahydrofuran (3 mL) at 0° C. After 0.5 h, 7-piperidin-4-yl-7,9-dihydro-8H-purin-8-one hydrochloride (73 mg, 0.248 mmol) and triethylamine (0.120 mL, 0.860 mmol) were added and the mixture allowed to warm to ambient temperature. After 18 h, the mixture was partitioned between ethyl acetate and water. The organic layer was washed with water (2×), saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane→95% dichloromethane/methanol) gave the title compound (114 mg). MS 567.2123 (M+1).

Workup

  1. waitAfter 18 h
  2. customthe mixture was partitioned between ethyl acetate and water
  3. washThe organic layer was washed with water (2×), saturated brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography (100% dichloromethane→95% dichloromethane/methanol)

Sources & evidence

ORD record
ord-fb13ff3f22c946b4b2a07d4db4c3482e
Source dataset
uspto-grants-2010_06
Patent number
US07745427B2

Reaction notes

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