1,2-Dichloroethane → 3-(Piperidin-1-yl)-N-[(1S,2S)-2-{[5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]pyridine-2-carboxamide

HRID 1750618Notes

Reaction equation

HRID 1750618 reaction equation
Cl.[F:2][C:3]([F:18])([F:17])[C:4]1[N:5]=[CH:6][C:7]([NH:10][C@H:11]2[CH2:15][CH2:14][CH2:13][C@@H:12]2[NH2:16])=[N:8][CH:9]=1.[N:19]1([C:25]2[C:26]([C:31](O)=[O:32])=[N:27][CH:28]=[CH:29][CH:30]=2)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1.N1C2C(=NC=CC=2)N(O)N=1.C(Cl)CCl.C(N(CC)CC)C>C(Cl)Cl>[N:19]1([C:25]2[C:26]([C:31]([NH:16][C@H:12]3[CH2:13][CH2:14][CH2:15][C@@H:11]3[NH:10][C:7]3[CH:6]=[N:5][C:4]([C:3]([F:2])([F:17])[F:18])=[CH:9][N:8]=3)=[O:32])=[N:27][CH:28]=[CH:29][CH:30]=2)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 181649HOAtHCID 185257313-(Piperidin-1-yl)picolinic acidHCID 118308118(1S,2S)-1-N-[5-(Trifluoromethyl)pyrazin-2-yl]cyclopentane-1,2-diamine hydrochloride2×

Product 1

HCID 1183082953-(Piperidin-1-yl)-N-[(1S,2S)-2-{[5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]pyridine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (1S,2S)-1-N-[5-(trifluoromethyl)pyrazin-2-yl]cyclopentane-1,2-diamine hydrochloride (Intermediate 14; 75 mg, 0.27 mmol), 3-(piperidin-1-yl)pyridine-2-carboxylic acid (CAS number 898289-01-5; 66 mg, 0.32 mmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (54 mg, 0.40 mmol), EDC (76 mg, 0.40 mmol) and triethylamine (0.111 ml, 0.80 mmol) in DCM (1 ml) was stirred at room temperature overnight. The reaction was partitioned between DCM and a saturated solution of sodium bicarbonate, filtered through a hydrophobic frit and concentrated in vacuo. The resulting residue was purified by column chromatography (silica, 40-100% ethyl acetate/petrol) and then further purified by reverse phase preparative HPLC (eluted with acetonitrile/water containing 0.1% ammonia) to afford the title compound.

Workup

  1. customThe reaction was partitioned between DCM
  2. filtrationa saturated solution of sodium bicarbonate, filtered through a hydrophobic frit
  3. concentrationconcentrated in vacuo
  4. customThe resulting residue was purified by column chromatography (silica, 40-100% ethyl acetate/petrol)
  5. customfurther purified by reverse phase preparative HPLC (eluted with acetonitrile/water containing 0.1% ammonia)

Sources & evidence

ORD record
ord-ad79b4bc30704b4c970480d91b47e20d
Source dataset
uspto-grants-2015_10
Patent number
US09156829B2

Reaction notes

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