2-Chloro-4-(tributylstannyl)pyrimidine → 3-(2-chloropyrimidin-4-yl)-N,N-dimethyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxamide

HRID 1529444Notes

Reaction equation

HRID 1529444 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]([N:13]([CH3:15])[CH3:14])=[O:12])[CH:9]=2)[N:4]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)[N:3]=1.[Cl:22][C:23]1[N:28]=[C:27]([Sn](CCCC)(CCCC)CCCC)[CH:26]=[CH:25][N:24]=1>CN(C=O)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:22][C:23]1[N:28]=[C:27]([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:11]([N:13]([CH3:15])[CH3:14])=[O:12])[CH:9]=3)[N:4]([CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][O:17]3)[N:3]=2)[CH:26]=[CH:25][N:24]=1

Participants

6

Reactant 2

HCID 468399532-Chloro-4-(tributylstannyl)pyrimidineHCID 679599763-iodo-N,N-dimethyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxamide

Product 1

HCID 867097953-(2-chloropyrimidin-4-yl)-N,N-dimethyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxamideYield 103.3%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3-iodo-N,N-dimethyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxamide (3 g, 7.53 mmol) and 2-chloro-4-(tributylstannyl)pyrimidine (3.6 g, 8.04 mmol) in DMF (35 mL) under argon atmosphere was added CuI (1.7 g, 9.02 mmol) and Pd(PPh3)4 (868.5 mg, 0.75 mmol) and argon gas was bubbled for 15 min. The reaction was heated at 100° C. for 1 h. The reaction was quenched with water to give off white precipitate. The suspension filtered, washed with water and dried. The crude was purified by neutral alumina column chromatography (eluting with 100% EtOAc) to give 3-(2-chloropyrimidin-4-yl)-N,N-dimethyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxamide (3.0 g, 58%) as an off white solid. MS (ESI, pos. ion) m/z: 386.2 (M+1).

Workup

  1. customwas bubbled for 15 min
  2. customThe reaction was quenched with water
  3. customto give off white precipitate
  4. filtrationThe suspension filtered
  5. washwashed with water
  6. customdried
  7. customThe crude was purified by neutral alumina column chromatography (eluting with 100% EtOAc)

Sources & evidence

ORD record
ord-26e7c3d818504ca88461cb725db222b8
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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