Diisopropylethylamine → [(3S,4R)-1-(5'-Cyano-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carbonyl)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl ester

HRID 527493Notes

Reaction equation

HRID 527493 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:25])[N:10]([CH2:23][CH3:24])[C@H:11]2[C@H:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[CH2:14][NH:13][CH2:12]2)=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[C:59]([C:61]1[CH:62]=[CH:63][C:64]([N:67]2[CH2:72][CH2:71][CH:70]([C:73](O)=[O:74])[CH2:69][CH2:68]2)=[N:65][CH:66]=1)#[N:60]>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:25])[N:10]([C@H:11]2[C@H:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[CH2:14][N:13]([C:73]([CH:70]3[CH2:69][CH2:68][N:67]([C:64]4[CH:63]=[CH:62][C:61]([C:59]#[N:60])=[CH:66][N:65]=4)[CH2:72][CH2:71]3)=[O:74])[CH2:12]2)[CH2:23][CH3:24])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 162274741-(5-Cyano-2-pyridinyl)-4-piperidinecarboxylic acidHCID 58312628ethyl-[(3S,4R)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-carbamic acid 4-fluoro-phenyl ester

Product 1

HCID 53246272[(3S,4R)-1-(5'-Cyano-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carbonyl)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl esterYield 63.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 125 mg (0.36 mmol) ethyl-[(3S,4R)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-carbamic acid 4-fluoro-phenyl ester, 137 mg (0.36 mmol) HATU, 63 uL (0.36 mmol) DIPEA and 69.4 mg (0.3 mmol) 5′-cyano-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carboxylic acid in 4 mL DMF was shaken for 2 h at room temperature. The mixture was subjected to purification by preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile, water and NEt3. The product containing fractions were evaporated to yield 106 mg (63%) of the title compound as off-white solid. MS m/e: 560.2 [M+H]+.

Workup

  1. customThe mixture was subjected to purification by preparative HPLC on reversed phase
  2. washeluting with a gradient
  3. customformed from acetonitrile, water and NEt3
  4. additionThe product containing fractions
  5. customwere evaporated

Sources & evidence

ORD record
ord-73cdaeee63e6462c85f901fc3e109094
Source dataset
uspto-grants-2016_05
Patent number
US09346786B2

Reaction notes

Loading…