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

HRID 1750716Notes

Reaction equation

HRID 1750716 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:11]2[N:16]=[CH:15][CH:14]=[CH:13][N:12]=2)=[C:6]([CH:10]=1)[C:7]([OH:9])=O.N1C2C(=NC=CC=2)N(O)N=1.C(Cl)CCl.C(N(CC)CC)C.Cl.[CH2:39]([C:41]1[C:42]([NH:51][C@H:52]2[CH2:56][CH2:55][CH2:54][C@@H:53]2[NH2:57])=[N:43][CH:44]=[C:45]([C:47]([F:50])([F:49])[F:48])[N:46]=1)[CH3:40]>C(Cl)Cl>[CH2:39]([C:41]1[C:42]([NH:51][C@H:52]2[CH2:56][CH2:55][CH2:54][C@@H:53]2[NH:57][C:7](=[O:9])[C:6]2[CH:10]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=2[C:11]2[N:16]=[CH:15][CH:14]=[CH:13][N:12]=2)=[N:43][CH:44]=[C:45]([C:47]([F:50])([F:48])[F:49])[N:46]=1)[CH3:40]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 181649HOAtHCID 670869505-Fluoro-2-(pyrimidin-2-yl)benzoic acidHCID 118308132(1S,2S)-1-N-[3-Ethyl-5-(trifluoromethyl)pyrazin-2-yl]cyclopentane-1,2-diamine hydrochloride2×

Product 1

HCID 91827608N-[(1S,2S)-2-{[3-Ethyl-5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]-5-fluoro-2-(pyrimidin-2-yl)benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-fluoro-2-(pyrimidin-2-yl)benzoic acid (CAS number 1293284-57-7; 53 mg, 0.24 mmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (33 mg, 0.24 mmol), EDC (46.3 mg, 0.241 mmol) and triethylamine (0.067 ml, 0.48 mmol) in DCM (5 ml) was added (1S,2S)-1-N-[3-ethyl-5-(trifluoromethyl)pyrazin-2-yl]cyclopentane-1,2-diamine hydrochloride (Intermediate 41; 50 mg, 0.161 mmol). The reaction mixture was stirred at room temperature for 88 hours and then partitioned between DCM and a saturated solution of sodium bicarbonate, passing through a hydrophobic frit. The organics were loaded directly on to a cation/anion mixed mode cartridge, eluted with DCM and concentrated in vacuo. This was then purified by reverse phase chromatography (C18 silica, 0-100% acetonitrile/water with 0.1% ammonia). The resulting aqueous was concentrated in vacuo and extracted with DCM. The organics were concentrated in vacuo to afford the title compound.

Workup

  1. custompartitioned between DCM
  2. additionmixed mode cartridge
  3. washeluted with DCM
  4. concentrationconcentrated in vacuo
  5. customThis was then purified by reverse phase chromatography (C18 silica, 0-100% acetonitrile/water with 0.1% ammonia)
  6. concentrationThe resulting aqueous was concentrated in vacuo
  7. extractionextracted with DCM
  8. concentrationThe organics were concentrated in vacuo

Sources & evidence

ORD record
ord-c3375234c59d46b38d9fa1a892e22a3f
Source dataset
uspto-grants-2015_10
Patent number
US09156829B2

Reaction notes

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