Triethylamine → HCID 178500476, compound

HRID 477866Notes

Reaction equation

HRID 477866 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:20][C:21]1[CH:40]=[CH:39][C:38](I)=[CH:37][C:22]=1[C:23]([NH:25][C@H:26]([C:33]([O:35][CH3:36])=[O:34])[CH2:27][CH2:28][C:29]([O:31][CH3:32])=[O:30])=[O:24].[C:42]([NH:48][C:49]1[N:50]=[C:51]([OH:61])[C:52]2[CH:58]=[C:57]([C:59]#[CH:60])[CH:56]=[N:55][C:53]=2[N:54]=1)(=[O:47])[C:43]([CH3:46])([CH3:45])[CH3:44].C(N(CC)CC)C>C(#N)C.[Pd](Cl)Cl.[Cu](I)I>[F:20][C:21]1[CH:40]=[CH:39][C:38]([C:60]#[C:59][C:57]2[CH:56]=[N:55][C:53]3[N:54]=[C:49]([NH:48][C:42](=[O:47])[C:43]([CH3:46])([CH3:44])[CH3:45])[N:50]=[C:51]([OH:61])[C:52]=3[CH:58]=2)=[CH:37][C:22]=1[C:23]([NH:25][C@H:26]([C:33]([O:35][CH3:36])=[O:34])[CH2:27][CH2:28][C:29]([O:31][CH3:32])=[O:30])=[O:24]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 14720609dimethyl N-(2-fluoro-5-iodobenzoyl)L-glutamateHCID 178437079HCID 178437079, compound

Product 1

HCID 178500476HCID 178500476, compoundYield 88%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 83717Copper iodideCatalystHCID 6342AcetonitrileSolvent2×

Procedure

A mixture of 0.016 g (0.093 mmol) of palladium chloride and 0.0486 g (0.185 mmol) of triphenylphosphine in 5 mL of acetonitrile is stirred under nitrogen at room temperature for 30 minutes. To this mixture is added an additional 10 mL of acetonitrile and 0.80 g (1.89 mmol) of dimethyl N-(2-fluoro-5-iodobenzoyl)L-glutamate, 0.50 g (1.85 mmol) of 2-pivaloylamino-4-hydroxy-6-ethynylpyrido[2,3-d]pyrimidine, 0.0088 g (0.046 mmol) of copper iodide, and 0.54 mL (3.89 mmol) of triethylamine. The mixture is then heated to reflux for 3 hours. After cooled to room temperature, the solvent is removed in vacuo and the residue is flash chromatographed on silica gel using 1:19 methanol:chloroform as the eluent to yield 0.92 g (88%) of dimethyl N-(2-fluoro-5-[2-(2-pivaloylamino-4-hydroxypyrido[2,3-d]pyrimidin-6-yl)-ethynyl]-benzoyl)-L-glutamate as a dark yellow solid m.p. 189°-191° C. (dec); Rf =0.48 (1:19 methanol:chloroform), Mass (FD)=565; IR (KBr, cm-1)=1146, 1228, 1263, 1440, 1488, 1549, 1596, 1607, 1622, 1673, 1742; UV (EtOH) λmax =319 (epsilon=30600), 259 (epsilon=11200), 212 (epsilon=42100); 1NMR (300 MHz, CDCl3) delta 1.38 (s, 9H), 2.19 (m, 1H), 2.3-2.6 (m, 3H), 3.72 (s, 3H), 3.85 (s, 3H), 4.95 (m, 1H), 7.21 (dd, 1H, J=8.5, 11.2 Hz), 7.45 (m, 1H), 7.68 (m, 1H), 8.26 (dd, 1H, J=2.0, 7.2 Hz), 8.37 (s, 1H), 8.63 (d, 1H, J=2.2 Hz), 9.0 (d, 1H, J=2.0 Hz).

Workup

  1. temperatureThe mixture is then heated
  2. temperatureto reflux for 3 hours
  3. temperatureAfter cooled to room temperature
  4. customthe solvent is removed in vacuo
  5. customchromatographed on silica gel using 1:19 methanol

Sources & evidence

ORD record
ord-0e1ca6d5b38f44c089b3538470dad34e
Source dataset
uspto-grants-1989_12
Patent number
US04889859

Reaction notes

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