Dichloromethane → 5-chloro-2-{4-[(1R,2S)-2-(2-{3-fluoro-4-[(5-methyl-1,3-oxazol-2-yl)methyl]phenoxy}ethyl)cyclopropyl]piperidin-1-yl}pyrimidine

HRID 1474744Notes

Reaction equation

HRID 1474744 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([C@H:14]3[CH2:16][C@H:15]3[CH2:17][CH2:18][O:19][C:20]3[CH:25]=[CH:24][C:23]([CH2:26][C:27]([NH:29][C:30]#[CH:31])=[O:28])=[C:22]([F:32])[CH:21]=3)[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[CH2:33](Cl)Cl>[Au](Cl)(Cl)Cl.C(#N)C>[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:9][CH2:10][CH:11]([C@H:14]3[CH2:16][C@H:15]3[CH2:17][CH2:18][O:19][C:20]3[CH:25]=[CH:24][C:23]([CH2:26][C:27]4[O:28][C:31]([CH3:33])=[CH:30][N:29]=4)=[C:22]([F:32])[CH:21]=3)[CH2:12][CH2:13]2)=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 6344DichloromethaneHCID 895841092-[4-(2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-fluorophenyl]-N-ethynylacetamide

Product 1

HCID 895839395-chloro-2-{4-[(1R,2S)-2-(2-{3-fluoro-4-[(5-methyl-1,3-oxazol-2-yl)methyl]phenoxy}ethyl)cyclopropyl]piperidin-1-yl}pyrimidine

Reagents, catalysts & solvents 2

HCID 26030Gold trichlorideCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-[4-(2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-fluorophenyl]-N-ethynylacetamide (20 mg, 0.042 mmol) in a 10:1 solution of DCM:acetonitrile (0.55 mL) was added gold chloride (˜1.3 mg, 0.004 mmol) and the resulting mixture stirred at room temperature for 2 days. The mixture was concentrated under reduced pressure. The material was purified using preparative RP-HPLC eluting with a gradient of 10-90% acetonitrile in water with 0.05% TFA buffer to afford the title compound. HPLC/MS; 1.52 min (2 minute run), 471 (M+H)+. GPR119 Human EC50: 2.5 nM

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customThe material was purified
  3. washusing preparative RP-HPLC eluting with a gradient of 10-90% acetonitrile in water with 0.05% TFA buffer

Sources & evidence

ORD record
ord-d5f40bbeb712488a8c0c046c9ac03101
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

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