4-Methylmorpholine → HCID 21899148, compound

HRID 1868619Notes

Reaction equation

HRID 1868619 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12]3[CH:13]=[CH:14][C:15]([CH2:17][N:18]4[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]4)=[CH:16][C:11]=3[N:10]=[C:9]2[NH2:24])[CH:5]=[CH:6][CH:7]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[F:49][C:50]([F:61])([F:60])[C:51]1[CH:52]=[C:53]([CH:57]=[CH:58][CH:59]=1)[C:54](O)=[O:55].O.ON1C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12]3[CH:13]=[CH:14][C:15]([CH2:17][N:18]4[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]4)=[CH:16][C:11]=3[N:10]=[C:9]2[NH:24][C:54](=[O:55])[C:53]2[CH:57]=[CH:58][CH:59]=[C:51]([C:50]([F:49])([F:60])[F:61])[CH:52]=2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 99633-(Trifluoromethyl)benzoic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27960291-Hydroxybenzotriazole hydrateHCID 534147611-(3-Fluorophenyl)-5-[(piperidin-1-yl)methyl]-1H-benzimidazol-2-amine

Product 1

HCID 21899148HCID 21899148, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-[1-(3-fluorophenyl)-5-piperidino-1-ylmethyl-1H-benzoimidazol-2-yl]-3-trifluoromethyl-benzamide: 500 mg 1-(3-fluorophenyl)-5-piperidin-1-ylmethyl-1H-benzoimidazol-2-ylamine (1.54 mmol, 1.0 equiv) was combined in a flask with 877 mg O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU, 2.32 mmol, 1.5 equiv), 440 mg 3-trifluoromethylbenzoic acid (2.32 mmol, 1.5 equiv) and 312 mg 1-hydroxybenzotriazole hydrate (HOBT, 2.32 mmol, 1.5 equiv) followed by the addition of 12 mL DMF and 254 μL N-methylmorpholine (NMM, 2.32 mmol, 1.5 equiv). The solution was allowed to stir for 24 h and then diluted with sat. Na2HCO3. The solution was extracted (2×10% MeOH/CH2Cl2), washed (1×brine), dried (NaSO4) and concentrated under reduced pressure. Purification by flash chromatography (SiO2, 5% MeOH/CH2Cl2) gave 0.2 g of the product as a tan solid (0.2 mmol). 1H NMR (DMSO-d6, 400 MHz) 13.0 (s, 1H), 8.35 (s, 1H), 8.30 (d, J=7.6 Hz, 1H), 7.88 (d, J=7.6 Hz, 1H), 7.72 (m, 3H), 7.62 (m, 2H), 7.47 (t, J=7.6 Hz, 1H), 7.22 (broad s, 2H), 3.55 (s, 2H), 2.38 (broad s, 4H), 1.5 (m, 6H).

Workup

  1. extractionThe solution was extracted (2×10% MeOH/CH2Cl2)
  2. washwashed (1×brine)
  3. dry with materialdried (NaSO4)
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash chromatography (SiO2, 5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-b129e2b5f9de402db28d5918d23d3a8f
Source dataset
uspto-grants-2009_12
Patent number
US07635774B2

Reaction notes

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