3-Chlorobenzamide → 3-Chloro-N-(6-chloro-4-(methyl(pyrimidin-5-yl)amino)pyridin-2-yl)benzamide

HRID 1045821Notes

Reaction equation

HRID 1045821 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]([CH3:15])[C:9]2[CH:10]=[N:11][CH:12]=[N:13][CH:14]=2)[CH:5]=[C:4]([Cl:16])[N:3]=1.[Cl:17][C:18]1[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=1)[C:21]([NH2:23])=[O:22].CC([O-])(C)C.[Na+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:17][C:18]1[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=1)[C:21]([NH:23][C:2]1[CH:7]=[C:6]([N:8]([CH3:15])[C:9]2[CH:10]=[N:11][CH:12]=[N:13][CH:14]=2)[CH:5]=[C:4]([Cl:16])[N:3]=1)=[O:22]

Participants

7

Reactant 4

HCID 692543-ChlorobenzamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 58349099N-(2,6-dichloropyridin-4-yl)-N-methylpyrimidin-5-amine

Product 1

HCID 510381603-Chloro-N-(6-chloro-4-(methyl(pyrimidin-5-yl)amino)pyridin-2-yl)benzamideYield 33%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

Compound 14 (43 mg, 0.17 mmol, 1.0 eq), 3-chlorobenzamide (39 mg, 0.25 mmol, 1.5 eq), NaOt-Bu (23 mg, 0.24 mmol, 1.4 eq), Pd(OAc)2 (1.9 mg, 0.0085 mmol, 0.050 eq) and Xantphos (10 mg, 0.017 mmol, 0.10 eq) were dissolved in toluene (1 mL) in a microwave vial. The vial was purged with argon, capped, and heated at 110° C. for 18 h. After cooling the reaction was filtered over a plug of celite and the plug was washed with 5% MeOH/CH2Cl2. The solvents were removed in vacuo and the crude mixture was purified by flash chromatography on silica gel afforded 21 mg (33%) of the title compound as a white solid: 1H NMR (400 MHz, CDCl3) δ 10.95 (s, 1H), 9.12 (s, 1H), 8.89 (s, 2H), 8.00 (t, J=1.8 Hz, 1H), 7.89 (m, 1H), 7.63 (ddd, J=8.1, 1.2, 0.9 Hz, 1H), 7.58 (d, J=2.1 Hz, 1H), 7.50 (t, J=7.9 Hz, 1H), 6.66 (d, J=2.0 Hz, 1H), 3.39 (s, 3H); [M+1]+: 374.1.

Workup

  1. customThe vial was purged with argon
  2. customcapped
  3. temperatureAfter cooling the reaction
  4. filtrationwas filtered over a plug of celite
  5. washthe plug was washed with 5% MeOH/CH2Cl2
  6. customThe solvents were removed in vacuo
  7. customthe crude mixture was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-add809fda8914254b90554f8297959ef
Source dataset
uspto-grants-2013_10
Patent number
US08569308B2

Reaction notes

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