Triethylamine → HCID 59722587, compound

HRID 1664894Notes

Reaction equation

HRID 1664894 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.Cl[C:33](OC1C=CC([N+]([O-])=O)=CC=1)=[O:34].[NH:45]1[CH2:50][CH2:49][CH:48]([N:51]2[CH2:57][CH2:56][C:55]3[CH:58]=[CH:59][CH:60]=[CH:61][C:54]=3[NH:53][C:52]2=[O:62])[CH2:47][CH2:46]1.C(=O)([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:33]([N:45]2[CH2:46][CH2:47][CH:48]([N:51]3[CH2:57][CH2:56][C:55]4[CH:58]=[CH:59][CH:60]=[CH:61][C:54]=4[NH:53][C:52]3=[O:62])[CH2:49][CH2:50]2)=[O:34])[CH2:18][CH2:17]1

Participants

7

Reactant 5

HCID 8471Triethylamine2×HCID 10340Sodium CarbonateHCID 821294-Nitrophenyl chloroformateHCID 113795873-(Piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-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 59722587HCID 59722587, compoundYield 71.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (7.0 μL, 0.05 mmol) was added to a solution 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 (17 mg, 0.05 mmol) and 4-nitrophenyl chloroformate (10.0 mg, 0.05 mmol) in tetrahydrofuran (3 mL) at 0° C. After 20 min, the hydrochloride salt of 3-piperidin-4-yl-1,3,4,5-tetrahydro-2H-1,3-benzodiazepin-2-one (14 mg, 0.05 mmol) and triethylamine (21 μL, 0.15 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 (3×). The organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane→93% dichloromethane/methanol) gave the title compound (22 mg). MS 617.2609 (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 silica gel chromatography (100% dichloromethane→93% dichloromethane/methanol)

Sources & evidence

ORD record
ord-e7efcc3686f1428590b6a0039b0f11db
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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