Pyridine → HCID 69067114, compound

HRID 1822018Notes

Reaction equation

HRID 1822018 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([O:8][C:9]2[CH:10]=[C:11]([NH2:15])[CH:12]=[CH:13][CH:14]=2)[CH2:4][CH2:3]1.N1C=CC=CC=1.[Cl:22][C:23]1[CH:31]=[CH:30][CH:29]=[CH:28][C:24]=1[C:25](Cl)=[O:26]>ClCCl>[ClH:22].[Cl:22][C:23]1[CH:31]=[CH:30][CH:29]=[CH:28][C:24]=1[C:25]([NH:15][C:11]1[CH:12]=[CH:13][CH:14]=[C:9]([O:8][CH:5]2[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]2)[CH:10]=1)=[O:26]

Participants

5

Reactant 3

HCID 1049PyridineHCID 691102-Chlorobenzoyl chlorideHCID 392026543-((1-Methylpiperidin-4-yl)oxy)aniline

Product 1

HCID 69067114HCID 69067114, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Combine 3-(1-methyl-piperidin-4-yloxy)-phenylamine (preparation 28, 185 mg, 0.90 mmol) in dichloromethane (9 mL), add pyridine (0.145 mL, 1.79 mmol) and stir at 0° C. for 5 min. Add 2-chloro-benzoyl chloride (0.142 mL, 1.12 mmol) and allow to warm to ambient temperature and stir. After 18 hr., dilute with dichloromethane (10 mL) and wash with sodium hydroxide (1N, 3×10 mL). Combine the organic layers, dry over sodium sulfate and concentrate under reduced pressure. Purify by flash chromatography, eluting with dichloromethane/ammonia (2.0 N in methanol) [20/1] to give the title compound as free base (112 mg, 36%). Dissolve the residue in diethyl ether and treat with ethereal hydrogen chloride (1.0 M). Triturate the resulting gum with ether to give the title compound as a white solid (115 mg). Mass spectrum (ion spray): m/z=345.1 (M+1); 1H NMR (free base, CDCl3): 7.88 (bs, N—H), 7.76 (dd, J=1.5 Hz, 7.3 Hz, 1H), 7.52 (bs, 1H), 7.47-7.36 (m, 3H), 7.28-7.24 (m, 2H), 7.03 (d, J=8.0 Hz, 1H), 6.72 (dd, J=8.2 Hz, 2.4 Hz, 1H), 4.48 (bs, 1H), 2.88-2.80 (bm, 2H), 2.66-2.56 (bm, 2H), 2.45 (s, 3H), 2.22-2.13 (bm, 2H), 2.01-1.92 (bm, 2H).

Workup

  1. temperatureto warm to ambient temperature
  2. stirringstir
  3. waitAfter 18 hr
  4. washwash with sodium hydroxide (1N, 3×10 mL)
  5. dry with materialCombine the organic layers, dry over sodium sulfate
  6. concentrationconcentrate under reduced pressure
  7. customPurify by flash chromatography
  8. washeluting with dichloromethane/ammonia (2.0 N in methanol) [20/1]

Sources & evidence

ORD record
ord-adff3e2fa8974116900894cf712e6808
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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