Triethylamine → HCID 59722556, compound

HRID 1664887Notes

Reaction equation

HRID 1664887 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]2[C:24]([C:27]([CH3:33])([O:29][CH2:30][CH2:31][OH:32])[CH3:28])=[CH:25][N:26]=[C:10]12.Cl[C:35](OC1C=CC([N+]([O-])=O)=CC=1)=[O:36].[NH:47]1[CH2:52][CH2:51][CH:50]([N:53]2[CH2:62][C:61]3[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=3)[NH:55][C:54]2=[O:63])[CH2:49][CH2:48]1.C(=O)([O-])[O-].[Na+].[Na+]>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]2[C:24]([C:27]([O:29][CH2:30][CH2:31][OH:32])([CH3:33])[CH3:28])=[CH:25][N:26]=[C:10]2[C@H:9]([NH:8][C:35]([N:47]2[CH2:48][CH2:49][CH:50]([N:53]3[CH2:62][C:61]4[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=4)[NH:55][C:54]3=[O:63])[CH2:51][CH2:52]2)=[O:36])[CH2:15][CH2:14]1

Participants

7

Reactant 5

HCID 8471Triethylamine2×HCID 10340Sodium CarbonateHCID 821294-Nitrophenyl chloroformateHCID 110425973-(Piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-oneHCID 59734938HCID 59734938, compound

Product 1

HCID 59722556HCID 59722556, compoundYield 33.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (5.0 μL, 0.037 mmol) was added to a solution of 2-{1-[(6S,9R)-9-amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-3-yl]-1-methylethoxy}ethanol (15.0 mg, 0.041 mmol) and 4-nitrophenyl chloroformate (9.0 mg, 0.045 mmol) in tetrahydrofuran (1 mL) at 0° C. After 15 min, 3-piperidin-4-yl-3,4-dihydroquinazolin-2(1H)-one (9.0 mg, 0.041 mmol) and triethylamine (17 μL, 0.12 mmol) were added and the mixture was allowed to warm to ambient temperature. After 1 h, saturated aqueous sodium carbonate was added and the mixture was extracted with dichloromethane (3×). The organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by reverse phase HPLC (95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid) gave the title compound (8.5 mg). MS 623.3163 (M+1).

Workup

  1. waitAfter 1 h
  2. extractionthe mixture was extracted with dichloromethane (3×)
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by reverse phase HPLC (95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-ee1af4b1cdb440b28fa370853436f14f
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

Loading…