Diethylamine → [(3S,4R)-1-[5'-(2-Diethylamino-acetyl)-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 527505Notes

Reaction equation

HRID 527505 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:42])[N:10]([C@H:13]2[C@H:17]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[CH2:16][N:15]([C:25]([CH:27]3[CH2:32][CH2:31][N:30]([C:33]4[CH:38]=[CH:37][C:36]([C:39](=[O:41])[CH3:40])=[CH:35][N:34]=4)[CH2:29][CH2:28]3)=[O:26])[CH2:14]2)[CH2:11][CH3:12])=[CH:4][CH:3]=1.BrC1(Br)C(=O)NC(=O)NC1=O.[CH2:54]([NH:56][CH2:57][CH3:58])[CH3:55]>O1CCOCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:42])[N:10]([C@H:13]2[C@H:17]([C:18]3[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=3)[CH2:16][N:15]([C:25]([CH:27]3[CH2:32][CH2:31][N:30]([C:33]4[CH:38]=[CH:37][C:36]([C:39](=[O:41])[CH2:40][N:56]([CH2:57][CH3:58])[CH2:54][CH3:55])=[CH:35][N:34]=4)[CH2:29][CH2:28]3)=[O:26])[CH2:14]2)[CH2:11][CH3:12])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8021DiethylamineHCID 948775,5-Dibromobarbituric acidHCID 53246385[(3S,4R)-1-(5'-Acetyl-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

Product 1

HCID 53246033[(3S,4R)-1-[5'-(2-Diethylamino-acetyl)-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 26.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 0.17 g (0.285 mmol) [(3S,4R)-1-(5′-Acetyl-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 (example 38) and 84.3 mg (0.295 mmol) 5,5-dibromobarbituric acid in 10 mL dioxane was heated to 85° C. for 40 h. At room temperature 0.216 g (2.95 mmol) diethylamine was added and heated to 45° C. for 2 h and evaporated. the residue was taken up in methanol and subjected to preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile, water and NEt3. The product containing fractions were evaporated to yield 49 mg (26%) of the title compound as light brown solid. MS m/e: 648.3 [M+H]+.

Workup

  1. temperatureheated to 45° C. for 2 h
  2. customevaporated
  3. washeluting with a gradient
  4. customformed from acetonitrile, water and NEt3
  5. additionThe product containing fractions
  6. customwere evaporated

Sources & evidence

ORD record
ord-e0916a1287564f24a00b239d271345bd
Source dataset
uspto-grants-2016_05
Patent number
US09346786B2

Reaction notes

Loading…