Triethylamine → HCID 135972971, compound

HRID 1664886Notes

Reaction equation

HRID 1664886 reaction equation
C(N(CC)CC)C.[F:8][C:9]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=1[C@H:16]1[CH2:22][N:21]2[C:23]([CH2:26][C:27]([F:30])([F:29])[F:28])=[CH:24][N:25]=[C:20]2[C@H:19]([NH2:31])[CH2:18][CH2:17]1.ClC(OC1C=CC([N+:42]([O-])=O)=CC=1)=O.[NH:45]1[CH2:50][CH2:49][CH:48]([N:51]2[CH2:60][C:59]3[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=3)[NH:53][C:52]2=[O:61])[CH2:47][CH2:46]1.[C:62](=[O:65])([O-])[O-].[Na+].[Na+]>O1CCCC1>[F:8][C:9]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=1[C@H:16]1[CH2:22][N:21]2[C:23]([CH2:26][C:27]([F:30])([F:28])[F:29])=[CH:24][N:25]=[C:20]2[C@H:19]([NH:31][C:62]([N:45]2[CH2:46][CH2:47][CH:48]([N:51]3[C:52](=[O:61])[NH:53][C:54]([C:59]4[CH:58]=[CH:57][CH:56]=[CH:55][CH:60]=4)=[N:42]3)[CH2:49][CH2:50]2)=[O:65])[CH2:18][CH2:17]1

Participants

7

Reactant 5

HCID 8471Triethylamine2×HCID 10340Sodium CarbonateHCID 821294-Nitrophenyl chloroformateHCID 110425973-(Piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-oneHCID 67438873(6S,9R)-6-(2,3-difluorophenyl)-3-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-amine

Product 1

HCID 135972971HCID 135972971, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (19 μL, 0.135 mmol) was added to a solution of the hydrochloride salt of (6S,9R)-6-(2,3-difluorophenyl)-3-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-amine (18.8 mg, 0.045 mmol) and 4-nitrophenyl chloroformate (9.0 mg, 0.045 mmol) in tetrahydrofuran (2 mL) at 0° C. After 1 h, 3-piperidin-4-yl-3,4-dihydroquinazolin-2(1H)-one (10 mg, 0.045 mmol) and triethylamine (19 μL, 0.135 mmol) were added and the mixture allowed to warm to ambient temperature. After 1 h, saturated aqueous sodium carbonate was added and the mixture was extracted with dichloromethane. The organic layer was washed with saturated aqueous sodium bicarbonate (3×), saturated brine, dried over sodium sulfate, filtered and concentrated. Purification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid) gave the title compound (7.8 mg). MS 603.2536 (M+1).

Workup

  1. waitAfter 1 h
  2. extractionthe mixture was extracted with dichloromethane
  3. washThe organic layer was washed with saturated aqueous sodium bicarbonate (3×), saturated brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-8bdafd6212684110bca8e90aeab58f9b
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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