Triethylamine → HCID 11498007, compound

HRID 1664910Notes

Reaction equation

HRID 1664910 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].[CH:45]1([C:48]2[CH:49]=[C:50]([CH:55]3[CH2:60][CH2:59][NH:58][CH2:57][CH2:56]3)[C:51](=[O:54])[NH:52][N:53]=2)[CH2:47][CH2:46]1.N1CCC(C2C(=O)NN=C(CCC)C=2)CC1.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[CH:45]1([C:48]2[CH:49]=[C:50]([CH:55]3[CH2:60][CH2:59][N:58]([C:33]([NH:31][C@@H:19]4[CH2:18][CH2:17][C@@H:16]([C:10]5[CH:11]=[CH:12][CH:13]=[C:14]([F:15])[C:9]=5[F:8])[CH2:22][N:21]5[C:23]([CH2:26][C:27]([F:30])([F:28])[F:29])=[CH:24][N:25]=[C:20]45)=[O:34])[CH2:57][CH2:56]3)[C:51](=[O:54])[NH:52][N:53]=2)[CH2:46][CH2:47]1

Participants

8

Reactant 6

HCID 8471Triethylamine2×HCID 10340Sodium CarbonateHCID 821294-Nitrophenyl chloroformateHCID 59722665HCID 59722665, compoundHCID 59722711HCID 59722711, compoundHCID 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 11498007HCID 11498007, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Triethylamine (34 μL, 0.24 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 (36 mg, 0.081 mmol) and 4-nitrophenyl chloroformate (16 mg, 0.081 mmol) in dichloromethane (1 mL) at 0° C. After 15 min, a solution of a mixture of 6-cyclopropyl-4-piperidin-4-ylpyridazin-3(2H)-one and 4-piperidin-4-yl-6-propylpyridazin-3(2H)-one (18 mg, 0.081 mmol) in dichloromethane (1 mL) and triethylamine (11 μL, 0.08 mmol) were added and the mixture allowed to warm to ambient temperature. After 3 h, saturated aqueous sodium carbonate was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate (3×), saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane→90% dichloromethane/methanol) gave 4-(6-cyclopropyl-3-oxo-2,3-dihydropyridazin-4-yl)-N-[(6S,9R)-6-(2,3-difluorophenyl)-3-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-yl]piperidine-1-carboxamide (11 mg); MS 591.2507 (M+1) and N-[(6S,9R)-6-(2,3-difluorophenyl)-3-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-yl]-4-(3-oxo-6-propyl-2,3-dihydropyridazin-4-yl)piperidine-1-carboxamide (14 mg); MS 593.2689 (M+1).

Workup

  1. additionwere added
  2. waitAfter 3 h
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated aqueous sodium bicarbonate (3×), saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography (100% dichloromethane→90% dichloromethane/methanol)

Sources & evidence

ORD record
ord-fb6a2481afa24fc99d5655499fe2a870
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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