2-Chloronicotinic acid → 2-Chloro-N-[1-(2,6-dichloro-pyridin-3-yl)-cyclopropylmethyl]nicotinamide

HRID 578877Notes

Reaction equation

HRID 578877 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2([CH2:11][NH2:12])[CH2:10][CH2:9]2)=[CH:6][CH:5]=[C:4]([Cl:13])[N:3]=1.FC(F)(F)C1C(C(O)=O)=NC=CC=1.CCN=C=NCCCN(C)C.Cl.C1C=C2N=NN(O)C2=CC=1.O.[Cl:50][C:51]1[C:56]([C:57](O)=[O:58])=[CH:55][CH:54]=[CH:53][N:52]=1>ClCCl.O.C(N(CC)CC)C>[Cl:50][C:51]1[N:52]=[CH:53][CH:54]=[CH:55][C:56]=1[C:57]([NH:12][CH2:11][C:8]1([C:7]2[C:2]([Cl:1])=[N:3][C:4]([Cl:13])=[CH:5][CH:6]=2)[CH2:9][CH2:10]1)=[O:58]

Participants

9

Reactant 5

HCID 762582-Chloronicotinic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 132338443-(Trifluoromethyl)pyridine-2-carboxylic acidHCID 89544422[1-(2,6-Dichloropyridin-3-yl)cyclopropyl]methanamine

Product 1

HCID 715588412-Chloro-N-[1-(2,6-dichloro-pyridin-3-yl)-cyclopropylmethyl]nicotinamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

0.45 ml of C-[1-(2,6-dichloro-pyridin-3-yl)-cyclopropyl]-methylamine was dissolved in 1.5 ml of dichloromethane under argon and 0.11 ml of triethylamine was added at ambient temperature. Ther reaction mixture was cooled at 0° C. and 383 mg of 3-(trifluoromethyl)pyridine-2-carboxylic acid, 145 mg of EDCI.HCl, 103 mg of HOBT hydrate and 59 mg of 2-chloropyridine-3-carboxylic acid were added sequentially. The reaction mixture was stirred at ambient temperature for 14 hours. Then water was added, the phases were separated and the aqueous phase was extracted with dichloromethane. The organic layers were combined, dried with anhydrous sodium sulphate, filtered and concentrated. Crude material was obtained as a yellow sticky solid, which was purified by trituration in diethyl ether to give 60 mg of the desired 2-Chloro-N-[1-(2,6-dichloro-pyridin-3-yl)-cyclopropylmethyl]nicotinamide as white solid. 1H-NMR (CDCl3): 8.45 ppm (m, 1H), 8.04 ppm (m, 1H), 7.68 ppm (d, 1H), 7.34 ppm (m, 1H), 6.53 ppm (m, 1H), 3.72 ppm (d, 2H), 1.19 ppm (m, 2H), 0.96 ppm (m, 2H).

Workup

  1. customthe phases were separated
  2. extractionthe aqueous phase was extracted with dichloromethane
  3. dry with materialdried with anhydrous sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customCrude material was obtained as a yellow sticky solid, which
  7. customwas purified by trituration in diethyl ether

Sources & evidence

ORD record
ord-7b8187907c6e474389e188ea231719e9
Source dataset
uspto-grants-2015_05
Patent number
US09040708B2

Reaction notes

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