Triphenylphosphine → 1-(azetidin-1-yl)-2-(2-fluoro-4-{2-[(1S,2R)-2-{1-[5-(methoxymethyl)pyridin-2-yl]piperidin-4-yl}cyclopropyl]ethoxy}phenyl)ethanone

HRID 1474738Notes

Reaction equation

HRID 1474738 reaction equation
CC(OC(/N=N/C(OC(C)C)=O)=O)C.[N:15]1([C:19](=[O:29])[CH2:20][C:21]2[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][C:22]=2[F:28])[CH2:18][CH2:17][CH2:16]1.[CH3:30][O:31][CH2:32][C:33]1[CH:34]=[CH:35][C:36]([N:39]2[CH2:44][CH2:43][CH:42]([C@H:45]3[CH2:47][C@H:46]3[CH2:48][CH2:49]O)[CH2:41][CH2:40]2)=[N:37][CH:38]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1>[N:15]1([C:19](=[O:29])[CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH2:49][CH2:48][C@@H:46]3[CH2:47][C@@H:45]3[CH:42]3[CH2:43][CH2:44][N:39]([C:36]4[CH:35]=[CH:34][C:33]([CH2:32][O:31][CH3:30])=[CH:38][N:37]=4)[CH2:40][CH2:41]3)=[CH:23][C:22]=2[F:28])[CH2:18][CH2:17][CH2:16]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 89582175HCID 89582175, compoundHCID 895841062-[(1S,2R)-2-{1-[5-(methoxymethyl)pyridin-2-yl]piperidin-4-yl}cyclopropyl]ethanol

Product 1

HCID 895839431-(azetidin-1-yl)-2-(2-fluoro-4-{2-[(1S,2R)-2-{1-[5-(methoxymethyl)pyridin-2-yl]piperidin-4-yl}cyclopropyl]ethoxy}phenyl)ethanone

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

DIAD (38.2 μl, 0.196 mmol) was added to a stirred mixture of 1-(azetidin-1-yl)-2-(2-fluoro-4-hydroxyphenyl)ethanone (41.1 mg, 0.196 mmol), 2-[(1S,2R)-2-{1-[5-(methoxymethyl)pyridin-2-yl]piperidin-4-yl}cyclopropyl]ethanol (57 mg, 0.196 mmol), and triphenyl phosphine (51.5 mg, 0.196 mmol) in toluene (327 μl). The mixture was degassed (3×) and stirred at RT for 2 hours. The mixture was diluted with ethyl acetate (20 mL), washed with water (20 ml), the layers separated, the aqueous phase extracted with EtOAc (20 ml), the organic fractions combined, washed with brine (35 ml), dried over sodium sulfate, filtered and the volatiles removed in vac. The residue was purified by column chromatography on silica gel, Biotage 25 g, using a gradient eluant of 0-100% EtOAc/hexanes to afford the title compound. LC/MS (m/z): 482 (M+H)+. GPR119 Human EC50: 0.94 nM

Workup

  1. customThe mixture was degassed (3×)
  2. additionThe mixture was diluted with ethyl acetate (20 mL)
  3. washwashed with water (20 ml)
  4. customthe layers separated
  5. extractionthe aqueous phase extracted with EtOAc (20 ml)
  6. washwashed with brine (35 ml)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customthe volatiles removed in vac
  10. customThe residue was purified by column chromatography on silica gel, Biotage 25 g

Sources & evidence

ORD record
ord-37760c8a2a6c48ef995b2a3092a0c91a
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

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