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

HRID 1474709Notes

Reaction equation

HRID 1474709 reaction equation
CC(OC(/N=N/C(OC(C)C)=O)=O)C.[OH:15][CH2:16][CH2:17][C@@H:18]1[CH2:20][C@@H:19]1[CH:21]1[CH2:26][CH2:25][N:24]([C:27]2[N:32]=[CH:31][C:30]([C:33]([OH:36])([CH3:35])[CH3:34])=[CH:29][N:28]=2)[CH2:23][CH2:22]1.[N:37]1([C:41](=[O:51])[CH2:42][C:43]2[CH:48]=[CH:47][C:46](O)=[CH:45][C:44]=2[F:50])[CH2:40][CH2:39][CH2:38]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[N:37]1([C:41](=[O:51])[CH2:42][C:43]2[CH:48]=[CH:47][C:46]([O:15][CH2:16][CH2:17][C@@H:18]3[CH2:20][C@@H:19]3[CH:21]3[CH2:26][CH2:25][N:24]([C:27]4[N:32]=[CH:31][C:30]([C:33]([OH:36])([CH3:34])[CH3:35])=[CH:29][N:28]=4)[CH2:23][CH2:22]3)=[CH:45][C:44]=2[F:50])[CH2:40][CH2:39][CH2:38]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 89582175HCID 89582175, compoundHCID 1176785602-(2-{4-[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl]piperidin-1-yl}pyrimidin-5-yl)propan-2-ol

Product 1

HCID 895840741-(azetidin-1-yl)-2-(2-fluoro-4-{2-[(1S,2R)-2-{1-[5-(2-hydroxypropan-2-yl]pyrimidin-2-yl]piperidin-4-yl}cyclopropyl]ethoxy}phenyl)ethanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

DIAD (95 μL, 0.491 mmol) was slowly added to a solution of 2-(2-{4-[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl]piperidin-1-yl}pyrimidin-5-yl)propan-2-ol (100 mg, 0.327 mmol), 1-(azetidin-1-yl)-2-(2-fluoro-4-hydroxyphenyl)ethanone (72 mg, 0.344 mmol), and triphenylphosphine (129 mg, 0.491 mmol) in DCM (1.6 mL). The mixture was stirred at rt for 3 hrs. The mixture was diluted with DCM (8 mL) and washed with 2 N NaOH solution (5 mL×1). The organic phase was dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by preparative TLC using 2×2000 micron silica preparative TLC plates (uv 254 active) which were developed using 100% EtOAc. The desired band (Rf=0.5 @ 100% EtOAc) was collected and extracted to give the title compound. 1H NMR (500 MHz, CD3CN) δ 8.41 (s, 2H), 7.17 (t, 1H), 6.72 (t, 2H), 4.68 (t, 2H), 4.19 (t, 2H), 4.06 (m, 2H), 3.91 (t, 211), 3.36 (s, 2H), 2.83 (t, 2H), 2.22 (m, 2H), 2.07 (m, 1H), 1.83 (m, 2H), 1.57 (m, 1H), 1.48 (s, 6H), 1.35-1.10 (m, 3H), 0.91 (m, 1H), 0.60 (m, 2H), −0.05 (m, 111). LC/MS (m/z): 497 (M+H)+, GPR119 Human EC50: 7.5 nM.

Workup

  1. washwashed with 2 N NaOH solution (5 mL×1)
  2. dry with materialThe organic phase was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by preparative TLC
  6. customThe desired band (Rf=0.5 @ 100% EtOAc) was collected
  7. extractionextracted

Sources & evidence

ORD record
ord-ac09822a4912427c8532d6811794ea36
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

Loading…