Triethylamine → (2S)-1-(2-(1-(2,4-difluorophenyl)-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]ox azepin-9-yl)pyrrolidine-2-carb oxamide

HRID 886397Notes

Reaction equation

HRID 886397 reaction equation
Cl[C:2]1[N:28]=[CH:27][C:5]2[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1)[CH:9]=[C:8]([C:14]1[N:15]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])[N:16]=[CH:17][N:18]=1)[N:7]=3.[NH:29]1[CH2:36][CH2:35][CH2:34][C@H:30]1[C:31]([NH2:33])=[O:32].C(N(CC)CC)C.[NH4+].[Cl-]>CN1CCCC1=O.ClCCl>[F:26][C:20]1[CH:21]=[C:22]([F:25])[CH:23]=[CH:24][C:19]=1[N:15]1[C:14]([C:8]2[N:7]=[C:6]3[C:5]4[CH:27]=[N:28][C:2]([N:29]5[CH2:36][CH2:35][CH2:34][C@H:30]5[C:31]([NH2:33])=[O:32])=[CH:3][C:4]=4[O:13][CH2:12][CH2:11][N:10]3[CH:9]=2)=[N:18][CH:17]=[N:16]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 111306L-ProlinamideHCID 582050058-Chloro-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulene

Product 1

HCID 58204509(2S)-1-(2-(1-(2,4-difluorophenyl)-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]ox azepin-9-yl)pyrrolidine-2-carb oxamideYield 39.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 8-Chloro-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulene (0.200 g, 0.499 mmol), L-prolinamide (0.171 g, 0.00150 mol) and Triethylamine (0.417 mL, 0.00299 mol) in N-Methylpyrrolidinone (5 mL) under N2 was heated to 150° C. overnight. The mixture was diluted with dichloromethane. Saturated NH4Cl was added and the mixture was extracted 3 times with dichloromethane. The organic phases were combined, dried with Na2SO4 and concentrated. The crude was purified by reverse-phase HPLC to obtain 94 mg (39% yield) of 378 as a light pink solid. MS (ESI+) 479.2. 1H NMR (400 MHz, DMSO) δ 8.35 (s, 1H), 8.18 (s, 1H), 7.86 (s, 1H), 7.69 (td, J=8.7, 6.0 Hz, 1H), 7.62-7.53 (m, 1H), 7.35-7.26 (m, 2H), 6.92 (br, 1H), 5.84 (s, 1H), 4.47-4.36 (m, 4H), 4.24 (d, J=7.4 Hz, 1H), 3.62-3.53 (m, 1H), 3.42-3.32 (m, 1H), 2.24-2.08 (m, 1H), 2.02-1.83 (m, 3H)

Workup

  1. extractionthe mixture was extracted 3 times with dichloromethane
  2. dry with materialdried with Na2SO4
  3. concentrationconcentrated
  4. customThe crude was purified by reverse-phase HPLC

Sources & evidence

ORD record
ord-60a7ca21a657455c94124f243d4adf3d
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

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