N-methyl-2-pyrrolidone → HCID 86732437, compound

HRID 1776408Notes

Reaction equation

HRID 1776408 reaction equation
Br[C:2]1[CH:32]=[C:31]([F:33])[C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]([C:16]3[N:21]=[C:20]([NH:22][C:23]4[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=4)[C:19]([O:29][CH3:30])=[CH:18][N:17]=3)=[N:8]2)=[C:4]([F:34])[CH:3]=1.C([Sn](CCCC)(CCCC)[C:40]([O:42][CH2:43][CH3:44])=[CH2:41])CCC.CN1CCCC1=O>C1(C)C=CC=CC=1.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:43]([O:42][C:40]([C:2]1[CH:3]=[C:4]([F:34])[C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]([C:16]3[N:21]=[C:20]([NH:22][C:23]4[CH:24]=[CH:25][N:26]=[CH:27][CH:28]=4)[C:19]([O:29][CH3:30])=[CH:18][N:17]=3)=[N:8]2)=[C:31]([F:33])[CH:32]=1)=[CH2:41])[CH3:44]

Participants

6

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 619414Stannane, tributyl(1-ethoxyethenyl)-3×HCID 71553449HCID 71553449, compound

Product 1

HCID 86732437HCID 86732437, compound

Reagents, catalysts & solvents 2

HCID 13169693Triphenylphosphine palladium dichlorideCatalyst3×HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

100 mg of 2-[1-(4-bromo-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amine (2-12-1, 0.191 mmol, 1 eq.) was suspended in dry toluol. 1.34 mg of dichloropalladium-triphenylphosphane (1:2) (0.002 mmol, 0.01 eq.) and 71 μl of tributyl(1-ethoxyethenyl)stannane (0.21 mmol, 1.2 eq.) were added. The mixture was stirred for 5 hours at 100° C. bath temperature and for 18 hours at 120° C. bath temperature. 5 mg of dichloropalladium-triphenylphosphane (1:2) (0.007 mmol, 0.035 eq.) and 140 μl of tributyl(1-ethoxyethenyl)stannane (0.42 mmol, 2.4 eq.) and 1 ml of 1-methylpyrrolidin-2-one were added. The solution was stirred for 3 days at 100° C. bath temperature. 5 mg of dichloropalladium-triphenylphosphane (1:2) (0.007 mmol, 0.035 eq.) and 140 μl of tributyl(1-ethoxyethenyl)stannane (0.42 mmol, 2.4 eq.) were added and stirred at 100° C. again for 22 hours. The reaction mixture was concentrated in vacuo and purified by flash chromatography to yield 119 mg (0.2 mmol, 107%) of the analytically pure target compound.

Workup

  1. waitfor 18 hours at 120° C. bath temperature
  2. stirringThe solution was stirred for 3 days at 100° C. bath temperature
  3. stirringstirred at 100° C. again for 22 hours
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. custompurified by flash chromatography
  6. customto yield 119 mg (0.2 mmol, 107%) of the analytically pure target compound

Sources & evidence

ORD record
ord-ad5faefd213d4f419bb1ae90e50eef9e
Source dataset
uspto-grants-2016_02
Patent number
US09265763B2

Reaction notes

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