Cesium fluoride → HCID 57832886, compound

HRID 729749Notes

Reaction equation

HRID 729749 reaction equation
Cl[C:2]1[C:7]([CH2:8][CH2:9][CH3:10])=[C:6]([N:11]2[CH2:16][CH2:15][CH:14]([C:17]3[N:26]=[C:25]4[C:20]([CH2:21][CH2:22][CH2:23][NH:24]4)=[CH:19][CH:18]=3)[CH2:13][CH2:12]2)[N:5]=[CH:4][N:3]=1.[CH3:27][C:28]([O:31][C:32](=[O:47])[C@H:33]([CH2:45][NH2:46])[NH:34][C:35]([O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:36])([CH3:30])[CH3:29].[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]>[CH3:30][C:28]([O:31][C:32](=[O:47])[C@H:33]([CH2:45][NH:46][C:2]1[C:7]([CH2:8][CH2:9][CH3:10])=[C:6]([N:11]2[CH2:16][CH2:15][CH:14]([C:17]3[N:26]=[C:25]4[C:20]([CH2:21][CH2:22][CH2:23][NH:24]4)=[CH:19][CH:18]=3)[CH2:13][CH2:12]2)[N:5]=[CH:4][N:3]=1)[NH:34][C:35]([O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:36])([CH3:27])[CH3:29]

Participants

7

Reactant 4

HCID 25953Cesium fluorideHCID 634876Binap, (A+-)-HCID 10803731(S)-tert-Butyl 3-amino-2-(((benzyloxy)carbonyl)amino)propanoateHCID 57832875HCID 57832875, compound

Product 1

HCID 57832886HCID 57832886, compoundYield 61%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of 600 mg (1.62 mmoles) of 4-chloro-5-propyl-6-[4-(1,2,3,4-tetrahydro-1,8-naphthyridin-7-yl)-1-piperidinyl]-pyrimidine, 590 mg (2 mmoles) of (1,1-dimethylethyl)3-amino-N-[(phenylmethoxy)carbonyl]alaninate (prepared according to J. Med. Chem. (2001), 44(8), 1158-1176), 380 mg (2.51 mmoles) of caesium fluoride, 76 mg (0.083 mmole) of tris(dibenzylideneacetone)dipalladium(0), 102 mg (0.163 mmole) of 2,2′-bis(diphenyl-phosphino)-1,1′-binaphthyl in 50 ml of dioxane are 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. 620 mg (Yield=61%) of expected product is obtained in the form of an amorphous yellow solid.

Workup

  1. temperatureare 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-f965b8b7d745426686e42a6ae2e29a33
Source dataset
uspto-grants-2009_09
Patent number
US07582640B2

Reaction notes

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