Triethylamine → HCID 11556119, compound

HRID 1664950Notes

Reaction equation

HRID 1664950 reaction equation
C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.[F:30][C:31]1[C:36]([F:37])=[CH:35][CH:34]=[CH:33][C:32]=1[CH:38]1[CH2:44][N:43]2[C:45]([CH2:48][C:49]([F:52])([F:51])[F:50])=[N:46][N:47]=[C:42]2[CH:41]([CH2:53][C:54](O)=[O:55])[CH2:40][CH2:39]1.[Cl-].[Cl-].[O:59]=[C:60]1[NH:68][C:63]2=[NH+:64][CH:65]=[CH:66][CH:67]=[C:62]2[N:61]1[CH:69]1[CH2:74][CH2:73][NH2+:72][CH2:71][CH2:70]1>C(#N)C.CN(C)C=O.C(OCC)(=O)C.C(=O)(O)[O-].[Na+]>[F:30][C:31]1[C:36]([F:37])=[CH:35][CH:34]=[CH:33][C:32]=1[CH:38]1[CH2:44][N:43]2[C:45]([CH2:48][C:49]([F:50])([F:52])[F:51])=[N:46][N:47]=[C:42]2[CH:41]([CH2:53][C:54]([N:72]2[CH2:71][CH2:70][CH:69]([N:61]3[C:62]4[C:63](=[N:64][CH:65]=[CH:66][CH:67]=4)[NH:68][C:60]3=[O:59])[CH2:74][CH2:73]2)=[O:55])[CH2:40][CH2:39]1

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67439871HCID 67439871, compoundHCID 178518668HCID 178518668, compound

Product 1

HCID 11556119HCID 11556119, compound

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Triethylamine (146 μL, 1.044 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (69 mg, 0.358 mmol), and 1-hydroxy-7-azabenzotriazole (41 mg, 0.298 mmol) were added to a solution of the hydrochloride salt of [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]acetic acid (127 mg, 0.298 mmol) and 2-oxo-1-piperidinium-4-yl-2,3-dihydro-1H-imidazo[4,5-b]pyridin-4-ium dichloride (87 mg, 0.298 mmol) in acetonitrile (3 mL) and N,N-dimethylformamide (1 mL). After 4 h, the reaction mixture was diluted with ethyl acetate and saturated aqueous sodium bicarbonate. The mixture was extracted with ethyl acetate, washed with saturated brine, dried with sodium sulfate, filtered and concentrated to give the title compound. Purification by reverse phase HPLC (100% water→100% acetonitrile with 0.1% trifluoroacetic acid) gave racemic cis compounds 1-(1-{[(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]acetyl}piperidin-4-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one and 1-(1-{[(6R,9S)-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]acetyl}piperidin-4-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one; MS 590.2299 (M+1), and racemic trans compounds 1-(1-{[(6S,9S)-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]acetyl}piperidin-4-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one and 1-(1-{[(6R,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]acetyl}piperidin-4-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one; MS 590.2293 (M+1). The trans enantiomers were separated by Chiralpak OD column (2×35 cm), 60% hexanes (0.1% diethylamine)/ethanol at 6 mL/min.

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. washwashed with saturated brine
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-3a32839952084607b48244dc3d13d21b
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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