1,2-Dichloroethane → N-[(1S,2S)-2-{[3-Ethyl-5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]-2-(3-methyl-1,2,4-oxadiazol-5-yl)benzamide

HRID 1750708Notes

Reaction equation

HRID 1750708 reaction equation
Cl.[CH2:2]([C:4]1[C:5]([NH:14][C@H:15]2[CH2:19][CH2:18][CH2:17][C@@H:16]2[NH2:20])=[N:6][CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[N:9]=1)[CH3:3].[CH3:21][C:22]1[N:26]=[C:25]([C:27]2[CH:35]=[CH:34][CH:33]=[CH:32][C:28]=2[C:29](O)=[O:30])[O:24][N:23]=1.N1C2C(=NC=CC=2)N(O)N=1.C(Cl)CCl.C(N(CC)CC)C>C(Cl)Cl>[CH2:2]([C:4]1[C:5]([NH:14][C@H:15]2[CH2:19][CH2:18][CH2:17][C@@H:16]2[NH:20][C:29](=[O:30])[C:28]2[CH:32]=[CH:33][CH:34]=[CH:35][C:27]=2[C:25]2[O:24][N:23]=[C:22]([CH3:21])[N:26]=2)=[N:6][CH:7]=[C:8]([C:10]([F:13])([F:11])[F:12])[N:9]=1)[CH3:3]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 181649HOAtHCID 231463052-(3-Methyl-1,2,4-oxadiazol-5-yl)benzoic acidHCID 118308132(1S,2S)-1-N-[3-Ethyl-5-(trifluoromethyl)pyrazin-2-yl]cyclopentane-1,2-diamine hydrochloride2×

Product 1

HCID 118308090N-[(1S,2S)-2-{[3-Ethyl-5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]-2-(3-methyl-1,2,4-oxadiazol-5-yl)benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (1S,2S)-1-N-[3-ethyl-5-(trifluoromethyl)pyrazin-2-yl]cyclopentane-1,2-diamine hydrochloride (Intermediate 41; 450 mg, 1.64 mmol), 2-(3-methyl-1,2,4-oxadiazol-5-yl)benzoic acid (CAS number 475105-77-2; 335 mg, 1.64 mmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (335 mg, 2.46 mmol), EDC (472 mg, 2.46 mmol) and triethylamine (0.687 ml, 4.92 mmol) in DCM (5 ml) was stirred at room temperature for 16 hours. The reaction was partitioned between DCM and a saturated solution of sodium bicarbonate, filtered through a hydrophobic frit and loaded directly on to a cation/anion mixed mode cartridge, eluted with DCM and concentrated in vacuo. The resulting residue was purified by reverse phase chromatography (C18 silica, 0-100% water (0.1% ammonia)/acetonitrile) and recrystalised from MTBE/heptane 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. additionmixed mode cartridge
  4. washeluted with DCM
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by reverse phase chromatography (C18 silica, 0-100% water (0.1% ammonia)/acetonitrile) and
  7. customrecrystalised from MTBE/heptane

Sources & evidence

ORD record
ord-fcd4922f319c4280aa08aa9963d2fabd
Source dataset
uspto-grants-2015_10
Patent number
US09156829B2

Reaction notes

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