2-(3-Methyl-1,2,4-oxadiazol-5-yl)benzoic acid → N-[(1S,2S)-2-{[3-Fluoro-5-(trifluoromethyl)pyridin-2-yl]amino}cyclopentyl]-2-(3-methyl-1,2,4-oxadiazol-5-yl)benzamide

HRID 1750699Notes

Reaction equation

HRID 1750699 reaction equation
C(OC1C=NC(C2C=CC=CC=2C(N[C@H]2CCC[C@@H]2NC2C=NC(C(F)(F)F)=CN=2)=O)=NC=1)C.Cl.[F:36][C:37]1[C:38]([NH:47][C@H:48]2[CH2:52][CH2:51][CH2:50][C@@H:49]2[NH2:53])=[N:39][CH:40]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:42]=1.[CH3:54][C:55]1[N:59]=[C:58]([C:60]2[CH:68]=[CH:67][CH:66]=[CH:65][C:61]=2[C:62](O)=[O:63])[O:57][N:56]=1>>[F:36][C:37]1[C:38]([NH:47][C@H:48]2[CH2:52][CH2:51][CH2:50][C@@H:49]2[NH:53][C:62](=[O:63])[C:61]2[CH:65]=[CH:66][CH:67]=[CH:68][C:60]=2[C:58]2[O:57][N:56]=[C:55]([CH3:54])[N:59]=2)=[N:39][CH:40]=[C:41]([C:43]([F:46])([F:44])[F:45])[CH:42]=1

Participants

4

Reactant 3

HCID 231463052-(3-Methyl-1,2,4-oxadiazol-5-yl)benzoic acidHCID 1183081672-(5-Ethoxypyrimidin-2-yl)-N-[(1S,2S)-2-{[5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]benzamideHCID 118308208(1S,2S)-1-N-[3-Fluoro-5-(trifluoromethyl)pyridin-2-yl]cyclopentane-1,2-diamine hydrochloride2×

Product 1

HCID 118308067N-[(1S,2S)-2-{[3-Fluoro-5-(trifluoromethyl)pyridin-2-yl]amino}cyclopentyl]-2-(3-methyl-1,2,4-oxadiazol-5-yl)benzamide

Procedure

Prepared according to the procedure for 2-(5-Ethoxypyrimidin-2-yl)-N-[(1S,2S)-2-{[5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]benzamide (Example 135) from (1S,2S)-1-N-[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]cyclopentane-1,2-diamine hydrochloride (Intermediate 34: 450 mg, 1.71 mmol) and 2-(3-methyl-1,2,4-oxadiazol-5-yl)benzoic acid (CAS number 475105-77-2; 349 mg, 1.71 mmol) except after the reaction was complete it was partitioned between DCM and a saturated solution of sodium bicarbonate, filtered through a hydrophobic frit. The organics were loaded directly on to a cation/anion mixed mode cartridge, eluted with DCM and concentrated in vacuo. The resulting residue was purified by column chromatography (silica, 0-100% ethyl acetate/petrol) and then purified by reverse phase column chromatography (C18 silica, 0-100% water (0.05% ammonia)/acetonitrile) to afford the title compound.

Workup

  1. customPrepared
  2. customwas partitioned between DCM
  3. filtrationa saturated solution of sodium bicarbonate, filtered through a hydrophobic frit
  4. additionmixed mode cartridge
  5. washeluted with DCM
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography (silica, 0-100% ethyl acetate/petrol)
  8. custompurified by reverse phase column chromatography (C18 silica, 0-100% water (0.05% ammonia)/acetonitrile)

Sources & evidence

ORD record
ord-0fbb631a56b24187a290a6b96d796632
Source dataset
uspto-grants-2015_10
Patent number
US09156829B2

Reaction notes

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