1,2-Dichloroethane → 2-Cyclopropyl-6-fluoro-N-[(1S,2S)-2-{[5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]benzamide

HRID 1750633Notes

Reaction equation

HRID 1750633 reaction equation
FC(F)C1C=CC=CC=1C(N[C@H]1CCC[C@@H]1NC1C=NC(C(F)(F)F)=CN=1)=O.Cl.[F:30][C:31]([F:46])([F:45])[C:32]1[N:33]=[CH:34][C:35]([NH:38][C@H:39]2[CH2:43][CH2:42][CH2:41][C@@H:40]2[NH2:44])=[N:36][CH:37]=1.[CH:47]1([C:50]2[CH:58]=[CH:57][CH:56]=[C:55]([F:59])[C:51]=2[C:52](O)=[O:53])[CH2:49][CH2:48]1.C(Cl)CCl.N1C2C(=NC=CC=2)N(O)N=1.C(N(CC)CC)C>>[CH:47]1([C:50]2[CH:58]=[CH:57][CH:56]=[C:55]([F:59])[C:51]=2[C:52]([NH:44][C@H:40]2[CH2:41][CH2:42][CH2:43][C@@H:39]2[NH:38][C:35]2[CH:34]=[N:33][C:32]([C:31]([F:30])([F:45])[F:46])=[CH:37][N:36]=2)=[O:53])[CH2:48][CH2:49]1

Participants

7

Reactant 6

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 181649HOAtHCID 1145603012-Cyclopropyl-6-fluorobenzoic acidHCID 118308118(1S,2S)-1-N-[5-(Trifluoromethyl)pyrazin-2-yl]cyclopentane-1,2-diamine hydrochloride2×HCID 1183081232-(Difluoromethyl)-N-[(1S,2S)-2-{[5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]benzamide

Product 1

HCID 1183081762-Cyclopropyl-6-fluoro-N-[(1S,2S)-2-{[5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]benzamide

Procedure

Prepared according to the procedure for 2-(difluoromethyl)-N-[(1S,2S)-2-{[5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]benzamide (Example 65) from (1S,2S)-1-N-[5-(trifluoromethyl)pyrazin-2-yl]cyclopentane-1,2-diamine hydrochloride (Intermediate 14; 100 mg, 0.35 mmol) and 2-cyclopropyl-6-fluorobenzoic acid (CAS number 1603213-26-8; 64 mg, 0.35 mmol) except to this was added EDC (68 mg, 0.354 mmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (48 mg, 0.35 mmol) and triethylamine (0.1 ml, 0.71 mmol) and the reaction was stirred at room temperature for a further 1 hour. The reaction mixture was partitioned between DCM and water, filtered through a hydrophobic frit and concentrated in vacuo. The resulting residue was purified by reverse phase preparative HPLC (eluted with acetonitrile/water containing 0.1% formic acid) and then triturated with heptane/diethyl ether to afford the title compound.

Workup

  1. customPrepared
  2. customThe reaction mixture was partitioned between DCM and water
  3. filtrationfiltered through a hydrophobic frit
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by reverse phase preparative HPLC (eluted with acetonitrile/water containing 0.1% formic acid)
  6. customtriturated with heptane/diethyl ether

Sources & evidence

ORD record
ord-5416046b1b6e4575881a1f02472ee872
Source dataset
uspto-grants-2015_10
Patent number
US09156829B2

Reaction notes

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