1-Methyl-5-(tri-n-butylstannyl)imidazole → HCID 71577057, compound

HRID 1630344Notes

Reaction equation

HRID 1630344 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:14]=[C:13]([NH:15][CH3:16])[C:12]([C:17]([F:20])([F:19])[F:18])=[CH:11][N:10]=2)=[C:4]([O:21][CH3:22])[CH:3]=1.[CH3:23][N:24]1[C:28]([Sn](CCCC)(CCCC)CCCC)=[CH:27][N:26]=[CH:25]1>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:22][O:21][C:4]1[CH:3]=[C:2]([C:28]2[N:24]([CH3:23])[CH:25]=[N:26][CH:27]=2)[CH:7]=[CH:6][C:5]=1[NH:8][C:9]1[N:14]=[C:13]([NH:15][CH3:16])[C:12]([C:17]([F:20])([F:19])[F:18])=[CH:11][N:10]=1

Participants

5

Reactant 2

HCID 109156511-Methyl-5-(tri-n-butylstannyl)imidazoleHCID 86688208HCID 86688208, compound

Product 1

HCID 71577057HCID 71577057, compoundYield 42.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of N2-(4-bromo-2-methoxyphenyl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine (0.151 g, 0.4 mmol), Pd(dppf)Cl2 (33 mg, 0.04 mmol) and 1-methyl-5-(tributylstannyl)-1H-imidazole (297 mg, 0.8 mmol) in dioxane (5 mL) was degassed under a stream of nitrogen for 10 min. The reaction tube was sealed and heated at 100° C. during 18 hours. The mixture was cooled and concentrated under reduced pressure. The residue was partitioned between ethyl acetate (20 mL) and water (20 mL) and the product extracted into ethyl acetate (2×20 mL). The combined organics were passed through a phase separation cartridge and the solvent removed under reduced pressure. Purification of the residue via preparative HPLC afforded N2-(2-methoxy-4-(1-methyl-1H-imidazol-5-yl)phenyl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine as a beige solid (64 mg, 42%). LCMS (10 cm_ESCI_Bicarb_MeCN): [MH+]=379 at 3.59 min. 1H NMR (400 MHz, DMSO): δ 8.33 (d, J=8.3, 1H); 8.21 (s, 1H); 8.10 (s, 1H); 7.72 (s, 1H); 7.23 (d, J=5.2, 1H); 7.16-7.07 (m, 3H); 3.95 (s, 3H); 3.74 (s, 3H); 2.96 (d, J=4.3, 3H).

Workup

  1. customwas degassed under a stream of nitrogen for 10 min
  2. customThe reaction tube was sealed
  3. temperatureThe mixture was cooled
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was partitioned between ethyl acetate (20 mL) and water (20 mL)
  6. extractionthe product extracted into ethyl acetate (2×20 mL)
  7. customThe combined organics were passed through a phase separation cartridge
  8. customthe solvent removed under reduced pressure
  9. customPurification of the residue via preparative HPLC

Sources & evidence

ORD record
ord-0aef1b175eab4e8e9a8aa94482fd05b7
Source dataset
uspto-grants-2014_07
Patent number
US08791130B2

Reaction notes

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