Pyridine → HCID 66938945, compound

HRID 1716910Notes

Reaction equation

HRID 1716910 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([NH2:16])[CH:11]=2)[CH3:9])[CH2:4][CH2:3]1.N1C=CC=CC=1.[F:23][C:24]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[C:25]=1[C:26]([Cl:28])=[O:27]>ClCCl>[ClH:28].[ClH:28].[F:23][C:24]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[C:25]=1[C:26]([NH:16][C:12]1[CH:13]=[CH:14][CH:15]=[C:10]([N:8]([CH3:9])[CH:5]2[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]2)[CH:11]=1)=[O:27]

Participants

5

Reactant 3

HCID 1049PyridineHCID 874382,6-Difluorobenzoyl chlorideHCID 43132687HCID 43132687, compound

Product 1

HCID 66938945HCID 66938945, compoundYield 106%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Combine 1-methyl-4-(N-(3-aminophenyl)-N-methylamino)piperidine (Preparation 11, 101 mg, 0.307 mmol), dichloromethane (6 mL) and pyridine (0.125 mL, 1.535 mmol) at 0° C. Add 2,6-difluorobenzoyl chloride (0.048 mL, 0.384 mmol) neat and continue stirring for 1 hr. Dilute with dichloromethane (5 mL) and wash with sodium hydroxide (1N aq., 2×8 mL). Combine the organic layers, dry over magnesium sulphate, filter under reduced pressure and concentrate to dryness. Purify by flash chromatography, eluting with a 20/1 mixture of dichloromethane/(2N ammonia in methanol) to give the free base of the title compound (88 mg, 80%). Following a salt formation method similar to that described in Example 1 gives the title compound as a yellow solid (89 mg): mass spectrum (free base, ion spray): m/z=360.1 (M+1), 1H NMR (free base, CDCl3): 7.56 (bs, 1H), 7.44-7.34 (m, 2H), 7.20 (t, J=8.2 Hz, 1H), 7.00 (t, J=8.2 Hz, 2H), 6.78 (d, J=8.0 Hz, 1H), 6.59 (dd, J=2.2 Hz, 8.2 Hz, 1H), 3.71-3.63 (bm, 1H), 3.14-3.04 (bm, 2H), 2.82 (s, 3H), 2.41 (bs, 3H), 2.11-1.97 (bm, 2H), 1.79 (bd, J=13 Hz, 2H).

Workup

  1. customat 0° C
  2. washwash with sodium hydroxide (1N aq., 2×8 mL)
  3. dry with materialCombine the organic layers, dry over magnesium sulphate
  4. filtrationfilter under reduced pressure
  5. concentrationconcentrate to dryness
  6. customPurify by flash chromatography
  7. washeluting with a 20/1 mixture of dichloromethane/(2N ammonia in methanol)

Sources & evidence

ORD record
ord-30d7d355a7af43289efab727fbf33ebf
Source dataset
uspto-grants-2010_09
Patent number
US07803813B2

Reaction notes

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