Ammonia → (1H-Benzoimidazol-5-yl)-(cis-2,3,4a,5,6,10b-hexahydro-1H-benzo[f]quinolin-4-yl)-methanone

HRID 521034Notes

Reaction equation

HRID 521034 reaction equation
F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[NH:47]1[C:51]2[CH:52]=[CH:53][C:54]([C:56]([OH:58])=O)=[CH:55][C:50]=2[N:49]=[CH:48]1.C(N(C(C)C)C(C)C)C.[CH2:68]1[C@H:77]2[C@H:72]([CH2:73][CH2:74][C:75]3[CH:81]=[CH:80][CH:79]=[CH:78][C:76]=32)[NH:71][CH2:70][CH2:69]1.N>CN(C)C=O.CO.C(OCC)(=O)C>[NH:47]1[C:51]2[CH:52]=[CH:53][C:54]([C:56]([N:71]3[C@@H:72]4[C@@H:77]([C:76]5[CH:78]=[CH:79][CH:80]=[CH:81][C:75]=5[CH2:74][CH2:73]4)[CH2:68][CH2:69][CH2:70]3)=[O:58])=[CH:55][C:50]=2[N:49]=[CH:48]1

Participants

10

Reactant 6

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12327022(4aS,10bR)-1,2,3,4,4a,5,6,10b-Octahydrobenzo[f]quinolineHCID 178524171HCID 178524171, compound

Product 1

HCID 178519358(1H-Benzoimidazol-5-yl)-(cis-2,3,4a,5,6,10b-hexahydro-1H-benzo[f]quinolin-4-yl)-methanone

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (0.50 g; alternatively, 2-(7-aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate may be used) is added to a solution of 1H-benzoimidazole-5-carboxylic acid (0.23 g) and ethyl-diisopropyl-amine (0.50 mL) in N,N-dimethylformamide (2 mL) at room temperature. The solution is stirred for 20 min prior to the addition of cis-1,2,3,4,4a,5,6,10b-octahydro-benzo[f]quinoline (0.30 g) dissolved in N,N-dimethylformamide (2 mL). The resulting solution is stirred at room temperature for 3 h. 32% aqueous ammonia (1 mL) in methanol (2 mL) is then added and the mixture is stirred for another 30 min. The mixture is diluted with ethyl acetate and washed with water and brine and dried (Na2SO4). The solvent is evaporated and the residue is chromatographed on silica gel (dichloromethane/methanol containing 1% NH3 95:5→80:20) to afford the title compound as a foam-like solid that is triturated with ether and dried to give a colorless solid [alternatively, the product may be purified by HPLC on reversed phase (MeOH/H2O)]. Yield: 0.38 g (80% of theory); LC (method 1): tR=2.53 min; Mass spectrum (ESI+): m/z=332 [M+H]+; 1H NMR (400 MHz, DMSO-d6, mixture of 2 rotamers) δ 1.52-1.82 (m, 4H), 1.82-1.94 (m, 1H), 2.24-ca. 2.48 (m, 1.5H), 2.71-3.02 (m, 3H), 3.03-3.18 (m, 0.5H), 3.50-3.65 (m, 0.5H), 3.88-4.05 (m, 0.5H), 4.39-4.56 (m, 0.5H), 4.83-4.99 (m, 0.5H), 6.89-7.20 (m, 4H), 7.21-7.27 (m, 1H), 7.56-7.70 (m, 2H), 8.23-8.35 (m, 1H), 12.58 (broad s, 1H).

Workup

  1. stirringThe resulting solution is stirred at room temperature for 3 h
  2. stirringthe mixture is stirred for another 30 min
  3. washwashed with water and brine
  4. dry with materialdried (Na2SO4)
  5. customThe solvent is evaporated
  6. customthe residue is chromatographed on silica gel (dichloromethane/methanol containing 1% NH3 95:5→80:20)

Sources & evidence

ORD record
ord-f32241eaccf7423885a7319e5774ea08
Source dataset
uspto-grants-2016_05
Patent number
US09328072B2

Reaction notes

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