Triethylamine → HCID 178450671, compound

HRID 1199818Notes

Reaction equation

HRID 1199818 reaction equation
[C:1]([NH:7][C:8]1[N:9]=[C:10]([OH:19])[C:11]2[CH:17]=[C:16](Br)[CH:15]=[N:14][C:12]=2[N:13]=1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[C:20]([C:22]1[CH:34]=[CH:33][C:25]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[CH:24][CH:23]=1)#[CH:21].C(N(CC)CC)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(#N)C.[Pd](Cl)Cl>[C:1]([NH:7][C:8]1[N:9]=[C:10]([OH:19])[C:11]2[CH:17]=[C:16]([C:21]#[C:20][C:22]3[CH:34]=[CH:33][C:25]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[CH:24][CH:23]=3)[CH:15]=[N:14][C:12]=2[N:13]=1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 13965008Tert-butyl 4-ethynylbenzoateHCID 178447249HCID 178447249, compound

Product 1

HCID 178450671HCID 178450671, compoundYield 69.5%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 6342AcetonitrileSolvent

Procedure

A mixture of 2.0 g of 2-pivaloylamino-4-hydroxy-6-bromopyrido[2,3-d]pyrimidine (prepared according to Example 6), 1.31 g of tert.-butyl 4-ethynylbenzoate, 2.57 ml of triethylamine, 0.11 g of palladium chloride, 0.32 g of triphenylphosphine, and 0.05 g of cuprous iodide in 150 ml of acetonitrile is heated at reflux under nitrogen for 2.5 hours. The reaction mixture is cooled to room temperature and then in an ice bath. The solid is collected and washed with small portions of cold acetonitrile to yield 1.91 g (69%) of 2-pivaloylamino-4-hydroxy-6-(4-tert.-butoxycarbonylphenylethynyl)pyrido[2,3-d]pyrimidine as a pale yellowish powder, which is sufficiently pure for the next reaction. A small sample of this solid, purified further by chromatography on silica gel using a 5% methanol:methylene chloride mixture as the eluent, had the following constants: m.p. >250° C.; NMR (CDCl3, 300 MHz) delta 1.37 (s, 9H), 1.63 (s, 9H), 7.61 (d, 2H, J=8.50 Hz), 8.02 (d, 2H, J=8.50 Hz), 8.42 (brs, 1H), 8.66 (slightly brs, 9.01 (slightly brs, 1H); IR (KBr) 3200, 2980, 1710, 1670, 1600, 1545, 1440, 1375, 1290, 1140, and 770 cm-1.

Workup

  1. temperatureis heated
  2. temperatureat reflux under nitrogen for 2.5 hours
  3. customThe solid is collected
  4. washwashed with small portions of cold acetonitrile

Sources & evidence

ORD record
ord-0b149c73eb394d7baa6c1cccd173f720
Source dataset
uspto-grants-1990_02
Patent number
US04902796

Reaction notes

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