Triethylamine → N-[(6S,9R)-6-(2,3-Difluorophenyl)-3-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-9-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide

HRID 1664929Notes

Reaction equation

HRID 1664929 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])=[N: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].[Cl-].[Cl-].[O:47]=[C:48]1[NH:56][C:51]2=[NH+:52][CH:53]=[CH:54][CH:55]=[C:50]2[N:49]1[CH:57]1[CH2:62][CH2:61][NH2+:60][CH2:59][CH2:58]1>O1CCCC1.ClCCl>[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])=[N:24][N:25]=[C:20]2[C@H:19]([NH:31][C:33]([N:60]2[CH2:61][CH2:62][CH:57]([N:49]3[C:50]4[C:51](=[N:52][CH:53]=[CH:54][CH:55]=4)[NH:56][C:48]3=[O:47])[CH2:58][CH2:59]2)=[O:34])[CH2:18][CH2:17]1

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 821294-Nitrophenyl chloroformateHCID 67439949(6S,9R)-6-(2,3-difluorophenyl)-3-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-9-amineHCID 178518668HCID 178518668, compound

Product 1

HCID 59722640N-[(6S,9R)-6-(2,3-Difluorophenyl)-3-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-9-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamideYield 54.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (58 μL, 0.417 mmol) was added to a solution of the bis hydrochloride salt of (6S,9R)-6-(2,3-difluorophenyl)-3-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-9-amine (50 mg, 0.119 mmol) and 4-nitrophenyl chloroformate (25 mg, 125 mmol) in tetrahydrofuran (4 mL) at 0° C. After 15 min, 2-oxo-1-piperidinium-4-yl-2,3-dihydro-1H-imidazo[4,5-b]pyridin-4-ium dichloride (52 mg, 0.179 mmol), triethylamine (58 μL, 0.417 mmol) and dichloromethane (3 mL) were added and the mixture allowed to warm to ambient temperature. After 5 h, the reaction was concentrated. Purification by reverse phase HPLC (C-18, 90% water/acetonitrile→100% acetonitrile with 0.1% trifluoroacetic acid) gave the title compound (38 mg). MS 591.2223 (M+1).

Workup

  1. waitAfter 5 h
  2. concentrationthe reaction was concentrated
  3. customPurification by reverse phase HPLC (C-18, 90% water/acetonitrile→100% acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-0efec826e8404d339e4350e95f1959c5
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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