2-Chloro-4-fluorobenzoyl chloride → 2-Chloro-N-[6-(1-cyclopropylmethyl-piperidin-4-yloxy)-pyridin-2-yl]-4-fluoro-benzamide

HRID 1822053Notes

Reaction equation

HRID 1822053 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4](Cl)=[O:5].[CH:12]1([CH2:15][N:16]2[CH2:21][CH2:20][CH:19]([O:22][C:23]3[N:28]=[C:27]([NH2:29])[CH:26]=[CH:25][CH:24]=3)[CH2:18][CH2:17]2)[CH2:14][CH2:13]1>N1C=CC=CC=1.C(Cl)Cl>[Cl:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([NH:29][C:27]1[CH:26]=[CH:25][CH:24]=[C:23]([O:22][CH:19]2[CH2:18][CH2:17][N:16]([CH2:15][CH:12]3[CH2:13][CH2:14]3)[CH2:21][CH2:20]2)[N:28]=1)=[O:5]

Participants

5

Reactant 2

HCID 27365462-Chloro-4-fluorobenzoyl chlorideHCID 578937436-(1-Cyclopropylmethyl-piperidin-4-yloxy)-pyridin-2-ylamine

Product 1

HCID 578936852-Chloro-N-[6-(1-cyclopropylmethyl-piperidin-4-yloxy)-pyridin-2-yl]-4-fluoro-benzamideYield 79.4%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolvent2×HCID 6344DichloromethaneSolvent

Procedure

Add 2-chloro-4-fluorobenzoyl chloride (149 mg, 0.58 mmol) to a solution of 6-(1-cyclopropylmethyl-piperidin-4-yloxy)-pyridin-2-ylamine (preparation 70, 130 mg, 0.53 mmol) in pyridine (7 mL) and beat at 55° C. for 15 hr. Remove pyridine in vacuo, dissolve the residue in CH2Cl2, wash with saturated NaHCO3 solution, dry over Na2SO4, filter and concentrate to give a residue. Chromatography (silica gel, eluting with 5% 2M NH3-Methanol in CH2Cl2) provides 170 mg (79%) of the title compound: mass spectrum (ion spray): 404.1 (M+1); 1H NMR (CDCl3, ppm): 8.08 (s, 1H), 7.63 (m, 2H), 7.52 (t, 1H), 7.11 (m, 1H), 6.99 (m, 1H), 6.41 (d, 1H), 4.82 (m, 1H), 2.72 (m, 2H), 2.26 (m, 2H), 2.17 (d, 2H), 1.89 (m, 2H), 1.69 (m, 2H), 0.77 (m, 1H), 0.40 (m, 2H), 0.00 (m, 2H). Hydrochloride salt: Analytical calc. for C21H23ClFN3O2.HCl.0.5H2O: C, 56.13; H, 5.61; N, 9.35. Found: C, 56.12; H, 5.30; N, 9.35.

Workup

  1. washwash with saturated NaHCO3 solution
  2. dry with materialdry over Na2SO4
  3. filtrationfilter
  4. concentrationconcentrate
  5. customto give a residue
  6. washChromatography (silica gel, eluting with 5% 2M NH3-Methanol in CH2Cl2)

Sources & evidence

ORD record
ord-d7b3342ee3c74b28a18255f3b2370975
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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