Cesium fluoride → HCID 57832866, compound

HRID 2358211Notes

Reaction equation

HRID 2358211 reaction equation
Cl[C:2]1[C:7]([CH2:8][CH:9]([CH3:11])[CH3:10])=[C:6]([N:12]2[CH2:17][CH2:16][CH:15]([C:18]3[N:27]=[C:26]4[C:21]([CH2:22][CH2:23][CH2:24][NH:25]4)=[CH:20][CH:19]=3)[CH2:14][CH2:13]2)[N:5]=[CH:4][N:3]=1.[NH2:28][CH2:29][C@@H:30]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[NH:31][C:32]([O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33].[F-].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:46][C:45]([O:44][C:42](=[O:43])[C@H:30]([CH2:29][NH:28][C:2]1[C:7]([CH2:8][CH:9]([CH3:11])[CH3:10])=[C:6]([N:12]2[CH2:17][CH2:16][CH:15]([C:18]3[N:27]=[C:26]4[C:21]([CH2:22][CH2:23][CH2:24][NH:25]4)=[CH:20][CH:19]=3)[CH2:14][CH2:13]2)[N:5]=[CH:4][N:3]=1)[NH:31][C:32]([O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33])([CH3:48])[CH3:47]

Participants

7

Reactant 4

HCID 25953Cesium fluorideHCID 634876Binap, (A+-)-HCID 10803731(S)-tert-Butyl 3-amino-2-(((benzyloxy)carbonyl)amino)propanoateHCID 57832830HCID 57832830, compound

Product 1

HCID 57832866HCID 57832866, compoundYield 83.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 450 mg (1.17 mmoles) of 4-chloro-5-isobutyl-6-[4-(1,2,3,4-tetrahydro-1,8-naphthyridin-7-yl)-1-piperidinyl]-pyrimidine, 413 mg (1.4 mmoles) of (1,1-dimethylethyl) 3-amino-N-[(phenylmethoxy)carbonyl]alaninate (prepared according to J. Med. Chem. (2001), 44(8), 1158-1176), 275 mg (1.81 mmoles) of caesium fluoride, 55 mg (0.060 mmole) of tris(dibenzylideneacetone)dipalladium(0), 75 mg (0.12 mmole) of 2,2′-bis(diphenyl-phosphino)-1,1′-binaphthyl in 35 ml of dioxane is heated under reflux for 20 hours. The reaction mixture is evaporated to dryness under reduced pressure (2 kPa) and the residue is taken up in ethyl acetate, water and a saturated solution of sodium bicarbonate. The organic phase is separated, dried over magnesium sulphate and the solvent is evaporated off under reduced pressure (2 kPa). The residue is chromatographed on alumina eluting with a gradient of methylene chloride-diisopropyl ether-ethyl acetate-methanol from 50-50-0-0 to 0-50-50-0 then 0-0-100-0 and finally 0-0-90-10. 630 mg (Yield=83%) of expected product is obtained in the form of an amorphous yellow solid.

Workup

  1. temperatureis heated
  2. temperatureunder reflux for 20 hours
  3. customThe reaction mixture is evaporated to dryness under reduced pressure (2 kPa)
  4. customThe organic phase is separated
  5. dry with materialdried over magnesium sulphate
  6. customthe solvent is evaporated off under reduced pressure (2 kPa)
  7. customThe residue is chromatographed on alumina eluting with a gradient of methylene chloride-diisopropyl ether-ethyl acetate-methanol from 50-50-0-0 to 0-50-50-0

Sources & evidence

ORD record
ord-8ecbbd9b471d4f7a972947e4b004f691
Source dataset
uspto-grants-2010_07
Patent number
US07763621B2

Reaction notes

Loading…