1,2-Dichloroethane → 2-[4-(2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-fluorophenyl]-N-ethynylacetamide

HRID 1474743Notes

Reaction equation

HRID 1474743 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]([OH:29])=O)=[C:22]([F:30])[CH:21]=3)[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[C:31]([NH2:33])#[CH:32].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C.O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[N:6][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]([NH:33][C:31]#[CH:32])=[O:29])=[C:22]([F:30])[CH:21]=3)[CH2:12][CH2:13]2)=[N:4][CH:3]=1

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 12979476EthynamineHCID 89583888[4-(2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-fluorophenyl]acetic acid

Product 1

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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of [4-(2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-fluorophenyl]acetic acid (80.0 mg, 0.184 mmol) and acetylenamine (11.68 mg, 0.190) in anhydrous DMF (1 mL) was added HOBt (28.2 mg, 0.184 mmol) followed by EDC (70.7 mg, 0.368 mmol) and the mixture was stirred at room temperature under nitrogen atmosphere for 16 hours. The mixture was diluted with water and ethyl acetate (5 mL). The layers were separated, the aqueous phase extracted with EtOAc (5 ml), the organic fractions combined, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified via preparative TLC plate (1000 μM) using 40% ethyl acetate in hexane. The band containing product was removed from the plate and the silica washed with EtOAc. The filtrate was collected and the volatiles removed in vacuo to afford the title compound. HPLC/MS; 1.49 min (2 minute run), 471 (M+H)+.

Workup

  1. customThe layers were separated
  2. extractionthe aqueous phase extracted with EtOAc (5 ml)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified via preparative TLC plate (1000 μM)
  7. additionThe band containing product
  8. customwas removed from the plate
  9. washthe silica washed with EtOAc
  10. customThe filtrate was collected
  11. customthe volatiles removed in vacuo

Sources & evidence

ORD record
ord-06ea3dda1e184c48bb58007479c02a7d
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

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