2-Bromopyrimidine → 3-ethyl-6-{1-[4-(methylsulfonyl)phenyl]-1H-pyrazol-5-yl}-1-pyrimidin-2-yl-1H-indazole

HRID 2113716Notes

Reaction equation

HRID 2113716 reaction equation
[CH2:1]([C:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[N:16]([C:17]4[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=4)[N:15]=[CH:14][CH:13]=3)=[CH:9][CH:10]=2)[NH:5][N:4]=1)[CH3:2].Br[C:28]1[N:33]=[CH:32][CH:31]=[CH:30][N:29]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[CH2:1]([C:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[N:16]([C:17]4[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=4)[N:15]=[CH:14][CH:13]=3)=[CH:9][CH:10]=2)[N:5]([C:28]2[N:33]=[CH:32][CH:31]=[CH:30][N:29]=2)[N:4]=1)[CH3:2]

Participants

7

Reactant 4

HCID 783452-BromopyrimidineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 178437987HCID 178437987, compound

Product 1

HCID 598107883-ethyl-6-{1-[4-(methylsulfonyl)phenyl]-1H-pyrazol-5-yl}-1-pyrimidin-2-yl-1H-indazoleYield 70%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

A mixture of 3-ethyl-6-{1-[4-(methylsulfonyl)phenyl]-1H-pyrazol-5-yl}-1H-indazole (50 mg, 0.14 mmol), tris(dibenzylideneacetone)dipalladium(0) (10 mg, 0.01 mmol), 2-bromopyrimidine (26 mg, 0.16 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (16 mg, 0.03 mmol), sodium tert-butoxide (19.7 mg, 0.21 mmol) and toluene (2.3 mL) was subjected to microwave irradiation (300 watts, 140° C.) for 300 seconds in a 10 mL sealed tube. The solvent was removed and the crude product absorbed onto silica gel. The residue was purified by column chromatography using as eluent 10% ethyl acetate in hexanes for 10 minutes, then a gradient to 50% ethyl acetate in hexanes at 20 minutes, then 50% for 5 minutes, then 100% at 35 minutes to provide 42 mg (70%) of 3-ethyl-6-{1-[4-(methylsulfonyl)phenyl]-1H-pyrazol-5-yl}-1-pyrimidin-2-yl-1H-indazole. LC/MS (EI) tR 3.82 (Method C), m/z 445.1 (M++1), 1H NMR (CDCl3) δ 1.5 (t, 3H); 3.0 (s, 3H); 3.1 (q, 2H); 6.6 (s, 1H); 7.1 (d, 2H); 7.6 (d, 2H); 7.7 (d, 1H); 7.8 (d, 1H); 7.9 (m, 2H); 8.7 (m, 3H).

Workup

  1. customwas subjected to microwave irradiation (300 watts, 140° C.) for 300 seconds in a 10 mL
  2. customsealed tube
  3. customThe solvent was removed
  4. customthe crude product absorbed onto silica gel
  5. customThe residue was purified by column chromatography
  6. customfor 10 minutes
  7. wait50% for 5 minutes

Sources & evidence

ORD record
ord-be99d8ccda9a4a3d9f11f2e87d895a9b
Source dataset
uspto-grants-2008_10
Patent number
US07432266B2

Reaction notes

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