1-methyl-5-(tributylstannyl)-1H-1,2,3-triazole → HCID 71577060, compound

HRID 1630351Notes

Reaction equation

HRID 1630351 reaction equation
Br[C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([NH:10][C:11]2[N:16]=[C:15]([NH:17][CH3:18])[C:14]([C:19]([F:22])([F:21])[F:20])=[CH:13][N:12]=2)=[C:4]([Cl:23])[CH:3]=1.[CH3:24][N:25]1[C:29]([Sn](CCCC)(CCCC)CCCC)=[CH:28][N:27]=[N:26]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]>[Cl:23][C:4]1[CH:3]=[C:2]([C:29]2[N:25]([CH3:24])[N:26]=[N:27][CH:28]=2)[C:7]([O:8][CH3:9])=[CH:6][C:5]=1[NH:10][C:11]1[N:16]=[C:15]([NH:17][CH3:18])[C:14]([C:19]([F:22])([F:21])[F:20])=[CH:13][N:12]=1

Participants

5

Reactant 2

HCID 226098261-methyl-5-(tributylstannyl)-1H-1,2,3-triazole3×HCID 86688212HCID 86688212, compound

Product 1

HCID 71577060HCID 71577060, compoundYield 44.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst3×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of N2-(4-bromo-2-chloro-5-methoxyphenyl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine (50 mg, 0.12 mmol), 1-methyl-5-(tributylstannyl)-1H-1,2,3-triazole (68 mg, 0.18 mmol) and Pd(dppf)2Cl2 (10 mg, 0.012 mmol) in dioxane (4 mL) was degassed under a stream of nitrogen for 10 min. The reaction mixture was heated to 100° C. for 18 h. Further amounts of 1-methyl-5-(tributylstannyl)-1H-1,2,3-triazole (68 mg, 0.18 mmol) and Pd(dppf)2Cl2 (10 mg, 0.012 mmol) were added and the mixture maintained at 100° C. for another 24 h, after which further amounts of 1-methyl-5-(tributylstannyl)-1H-1,2,3-triazole (68 mg, 0.18 mmol) and Pd(dppf)2Cl2 (10 mg, 0.012 mmol) were added. The mixture was maintained at 100° C. for another 48 h. The mixture was cooled and concentrated to dryness under vacuum, and the residue partitioned between DCM and water. The separated organic phase was concentrated to dryness under vacuum and the residue purified by RP-HPLC; the product was isolated as a cream solid (22 mg, 44%). LCMS (ESCI_Formic_MeCN): [MH+]=414 at 3.45 min. 1H NMR δ (DMSO-d6): 8.58 (s, 1H); 8.16 (s, 1H); 7.98 (s, 1H); 7.71 (s, 1H); 7.42 (s, 1H); 7.24 (d, J=5.1, 1H); 3.82 (s, 3H); 3.76 (s, 3H); 2.87 (d, J=4.4, 3H).

Workup

  1. customwas degassed under a stream of nitrogen for 10 min
  2. temperaturethe mixture maintained at 100° C. for another 24 h
  3. temperatureThe mixture was maintained at 100° C. for another 48 h
  4. temperatureThe mixture was cooled
  5. concentrationconcentrated to dryness under vacuum
  6. customthe residue partitioned between DCM and water
  7. concentrationThe separated organic phase was concentrated to dryness under vacuum
  8. customthe residue purified by RP-HPLC

Sources & evidence

ORD record
ord-c74a671295264552a270e1911d55cefd
Source dataset
uspto-grants-2014_07
Patent number
US08791130B2

Reaction notes

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