Potassium Carbonate → N-(tert-butyl)-5-(4-(((2-methylthiazol-4-yl)methyl)amino)-5-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide

HRID 2170176Notes

Reaction equation

HRID 2170176 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]2[N:11]=[C:12]([CH3:15])[S:13][CH:14]=2)[C:5]2=[C:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:17]=[CH:18][N:4]2[N:3]=1.[C:25]([NH:29][S:30]([C:33]1[CH:34]=[N:35][CH:36]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH:38]=1)(=[O:32])=[O:31])([CH3:28])([CH3:27])[CH3:26].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.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].C(Cl)Cl>[C:25]([NH:29][S:30]([C:33]1[CH:34]=[N:35][CH:36]=[C:37]([C:2]2[N:7]=[C:6]([NH:8][CH2:9][C:10]3[N:11]=[C:12]([CH3:15])[S:13][CH:14]=3)[C:5]3=[C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH:17]=[CH:18][N:4]3[N:3]=2)[CH:38]=1)(=[O:32])=[O:31])([CH3:28])([CH3:26])[CH3:27]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 903863802-Chloro-N-((2-methylthiazol-4-yl)methyl)-5-phenylpyrrolo[2,1-f][1,2,4]triazin-4-amineHCID 90386425N-(tert-Butyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-sulfonamide

Product 1

HCID 90386066N-(tert-butyl)-5-(4-(((2-methylthiazol-4-yl)methyl)amino)-5-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamideYield 33.3%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

2-Chloro-N-((2-methylthiazol-4-yl)methyl)-5-phenylpyrrolo[2,1-f][1,2,4]triazin-4-amine (0.300 g, 0.843 mmol) and N-(tert-butyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-sulfonamide (0.574 g, 1.69 mmol) were dissolved in dioxane (25 mL) and water (3 mL). To the reaction mixture was added K2CO3 (0.350 g, 2.53 mmol) and the reaction mixture was degassed with nitrogen for 15 minutes. PdCl2(dppf)-CH2Cl2 (69.0 mg, 0.0840 mmol) was added and the resulting reaction mixture degassed with nitrogen for 20 minutes then heated to reflux at 110° C. for 14 h. The reaction mixture was allowed to cool and concentrated under reduced pressure. The residue was diluted with CH2Cl2 (2×25 mL) and filtered through CELITE®. The filtrate was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using CombiFlash (REDISEP®, silica gel, 40 g, 25% EtOAc/hexanes) to afford N-(tert-butyl)-5-(4-(((2-methylthiazol-4-yl)methyl)amino)-5-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide (0.150 g, 28.0%). LCMS Condition B-82: retention time 2.35 min, [M+1]=534.2. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.15 (s, 9H), 2.62 (m, 3H), 4.88 (d, J=4.8 Hz, 2H), 6.75 (t, J=5.2 Hz, 1H), 6.85 (d, J=2.8 Hz, 1H), 7.36 (s, 1H), 7.42-7.57 (m, 5H), 7.94-7.97 (m, 2H) 8.91 (dd, J=2.0 Hz, J=2.4 Hz, 1H), 9.06 (d, J=2.4 Hz, 1H), 9.57 (d, J=2.0 Hz, 1H).

Workup

  1. customthe reaction mixture was degassed with nitrogen for 15 minutes
  2. customthe resulting reaction mixture
  3. customdegassed with nitrogen for 20 minutes
  4. temperaturethen heated
  5. temperatureto cool
  6. concentrationconcentrated under reduced pressure
  7. additionThe residue was diluted with CH2Cl2 (2×25 mL)
  8. filtrationfiltered through CELITE®
  9. dry with materialThe filtrate was dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-8e81dcbeeb374e71bbb1fe901cb9bcf5
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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