Tri-o-tolylphosphine → HCID 178471560, compound

HRID 1639243

Reaction equation

HRID 1639243 reaction equation
[C:1]([NH:7][C:8]1[N:9]=[C:10]([OH:28])[C:11]2[CH:17]=[C:16]([CH:18]=[CH:19][CH2:20][O:21][CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][O:23]3)[CH:15]=[N:14][C:12]=2[N:13]=1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].I[C:30]1[CH:51]=[CH:50][C:33]([C:34]([NH:36][C@H:37]([C:45]([O:47][CH2:48][CH3:49])=[O:46])[CH2:38][CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])=[O:35])=[CH:32][CH:31]=1.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(N(CC)CC)C.C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[O:23]1[CH2:24][CH2:25][CH2:26][CH2:27][CH:22]1[O:21][CH2:20][C:19]([C:30]1[CH:51]=[CH:50][C:33]([C:34]([NH:36][C@H:37]([C:45]([O:47][CH2:48][CH3:49])=[O:46])[CH2:38][CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])=[O:35])=[CH:32][CH:31]=1)=[CH:18][C:16]1[CH:15]=[N:14][C:12]2[N:13]=[C:8]([NH:7][C:1](=[O:6])[C:2]([CH3:4])([CH3:5])[CH3:3])[N:9]=[C:10]([OH:28])[C:11]=2[CH:17]=1

Participants

7

Reactant 3

HCID 80271Tri-o-tolylphosphineHCID 1885228diethyl (2S)-2-[(4-iodobenzoyl)amino]pentanedioate2×HCID 178447254HCID 178447254, compound

Product 1

HCID 178471560HCID 178471560, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Procedure

A mixture containing 3.48 g (9 mm) of 2-pivaloylamino-4-hydroxy-6-(3-tetrahydropyr-2-yloxyprop-1-en-1-yl)-pyrido[2,3-d]pyrimidine, 3.12 g, (1.2 equiv.) of diethyl N-(4-iodobenzoyl)glutamate, 546 mg (20%) of tris(2-methylphenyl)phosphine, 201 mg (10%) of palladium acetate and 85.5 mg (5%) of cuprous iodide in 15 ml of triethylamine and 240 ml of acetonitrile was heated at reflux under nitrogen. After 12 hours., 1.17 g of diethyl N-(4-iodobenzoyl)glutamate was added and the reaction mixture was heated at reflux under nitrogen for an additional 12 hours. The reaction mixture then was concentrated under reduced pressure and the residue was chromatographed on silica gel, eluting with 20:1 ethyl acetate:hexane. (Recovered starting material can be recycled through the foregoing procedure.) The concentrated material was dissolved in 1:5 ethyl acetate:ether and this solution was refrigerated for 15 hours. The solid which formed was collected by filtration, washed with cold ethyl acetate and dried to yield diethyl N-[4-{1-(tetrahydropyr-2-yloxy)-3-(2-pivaloylamino-4-hydroxypyrido[2,3-d]pyrimidin-6-yl)prop-2-en-2-yl}benzoyl]glutamate. mp. 273°-275° C. Analysis calculated for C36H45N4O9 ; C, 62.50; H, 6.56; N, 10.12. Found: C, 62.21; H, 6.34; N, 9.83. NMR (CDCL3), delta, 1.24 (t, 3H, J=7 Hz), 1.32 (t 3H, J=7 Hz), 1.32 (s, 9H), 1.53-1.87 (m, 6H), 2.11-2.22 (m, 1H), 2.29-2.41 (m 1H), 2.42-2.58 (m, 2H), 3.53-3.59 (m, 1H), 3.80-3.88 (m, 1H), 4.13 (q, 2H, J=7 Hz), 4.25 (q, 2H, J=7 Hz), 4.33 (d, 1H, J=14 Hz), 4.62 (d, 1H, J=14 Hz), 4.75-4.83 (m, 2H), 6.84 (s, 1H), 7.12 (brs, 1H, NH, J =7 Hz), 7.31 (d, 2H, J=8.1 Hz), 7.79 (d, 2H, J=8.1 Hz), 8.13 (d, 1H, J=1.6 Hz), 8.34 (brs, NH), 8.42 (d, 1H, J=1.6 Hz), 11.99 (brs, NH).

Workup

  1. temperaturewas heated
  2. temperatureat reflux under nitrogen
  3. temperaturethe reaction mixture was heated
  4. temperatureat reflux under nitrogen for an additional 12 hours
  5. concentrationThe reaction mixture then was concentrated under reduced pressure
  6. customthe residue was chromatographed on silica gel
  7. washeluting with 20:1 ethyl acetate
  8. custom(Recovered
  9. dissolution) The concentrated material was dissolved in 1:5 ethyl acetate
  10. waitether and this solution was refrigerated for 15 hours
  11. customThe solid which formed
  12. filtrationwas collected by filtration
  13. washwashed with cold ethyl acetate
  14. customdried

Sources & evidence

ORD record
ord-001076e4e5e546a8a007a4d5eb067dff
Source dataset
uspto-grants-1989_11
Patent number
US04883799

Linked notes

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