Triethylamine → HCID 178471557, compound

HRID 704867Notes

Reaction equation

HRID 704867 reaction equation
Br[C:2]1[CH:19]=[N:18][C:5]2[N:6]=[C:7]([NH:11][C:12](=[O:17])[C:13]([CH3:16])([CH3:15])[CH3:14])[N:8]=[C:9]([OH:10])[C:4]=2[CH:3]=1.[C:20]([C:22]1[CH:43]=[CH:42][C:25]([C:26]([NH:28][C@H:29]([C:37]([O:39][CH2:40][CH3:41])=[O:38])[CH2:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])=[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:12]([NH:11][C:7]1[N:8]=[C:9]([OH:10])[C:4]2[CH:3]=[C:2]([C:21]#[C:20][C:22]3[CH:23]=[CH:24][C:25]([C:26]([NH:28][C@H:29]([C:37]([O:39][CH2:40][CH3:41])=[O:38])[CH2:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])=[O:27])=[CH:42][CH:43]=3)[CH:19]=[N:18][C:5]=2[N:6]=1)(=[O:17])[C:13]([CH3:16])([CH3:15])[CH3:14]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 10936456Diethyl N-(4-ethynylbenzoyl)-L-glutamateHCID 178447249HCID 178447249, compound

Product 1

HCID 178471557HCID 178471557, compoundYield 53.9%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 6342AcetonitrileSolvent

Procedure

A mixture of 2.0 g of 6-bromo-2-pivaloylamino-4-hydroxypyrido[2,3-d]pyrimidine, 2.1 g of diethyl N-(4-ethynylbenzoyl)-L-glutamate, 2.57 ml of triethylamine, 0.11 g of palladium chloride, 0.32 g of triphenylphosphine, and 0.05 g of cuprous chloride in 150 ml of acetonitrile is heated at reflux under nitrogen for 2.5 hours. The solid which forms upon first cooling to room temperature is collected by filtration, and washed with cold acetronitrile to yield 1.91 g of diethyl N-[4-(2-pivaloylamino-4-hydroxypyrido[2,3-d]pyrimidin-6-ylethynyl)benzoyl]-L-glutamate which is sufficiently pure for further processing. Chromatography on silica gel with 5% methanol:methylene chloride showing the following physical properties. m.p. >250° C.; NMR (CDCl3, 300 MHz) delta 1.25 (t, 3H, J=7.20 Hz), 1.33 (t, 3H, J=7.20 Hz), 1.36 (s, 9H), 2.14-2.62 (m, 4H), 4.14 (q, 2H, J= 7.20 Hz), 4.27 (q, 2H, J=7.20 Hz), 4.79-4.86 (m, 1H), 7.30 (d, 1H, J=8.40 Hz), 7.63 (d, 2H, J=8.25 Hz), 7.86 (d, 2H, J=8.25 Hz), 8.51 (brs, 1H), 8.64 (d, 1H, J=2.40 Hz), 8.97 (d, 1H, J=2.40 Hz), 12.2 (brs, 1H); IR (KBr) 3330, 3290, 2970, 1730, 1655, 1590, 1530, 1440, 1370, 1260, 1140, 1020, 965, 925, 850, 810, and 760 cm1 ; 13C-NMR (CDCl3, 75 MHz) delta 14.3, 27.1, 27.2, 30.7, 40.6, 52.7, 61.1, 62.0, 87.61, 92.71, 115.1, 117.3, 125.9, 127.4, 127.5, 132.0, 133.9, 138.7, 149.6, 157.8, 158.6, 160.5, 166.4 172.1, 173.5, 180.8. Anal. Calcd. for C30H33N5O7 : C, 62.60; H, 5.78; N, 12.35. Found: C, 44.56; H, 3.85; N, 17.30; Br, 24.38.

Workup

  1. temperatureis heated
  2. temperatureat reflux under nitrogen for 2.5 hours
  3. filtrationis collected by filtration
  4. washwashed with cold acetronitrile

Sources & evidence

ORD record
ord-dd99719b15ff4abaa05982319705d665
Source dataset
uspto-grants-1991_01
Patent number
US04988813

Reaction notes

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