2-Methyl-3-buten-2-ol → HCID 22291506, compound

HRID 968124Notes

Reaction equation

HRID 968124 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:15]4[CH:17]=[C:18]([NH:21][C:22](=[O:30])[C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=5[Cl:29])[CH:19]=[CH:20][C:14]=4[CH2:13][CH2:12][C:11]=3[C:10]([C:31]([NH2:33])=[O:32])=[N:9]2)=[CH:4][CH:3]=1.C1(C2C=CC=CC=2)C=CC=CC=1P(C(C)(C)C)C(C)(C)C.[CH3:55][C:56]([OH:60])([CH:58]=[CH2:59])[CH3:57].C(N(CC)CC)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C=O>[Cl:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[C:22]([NH:21][C:18]1[CH:19]=[CH:20][C:14]2[CH2:13][CH2:12][C:11]3[C:10]([C:31]([NH2:33])=[O:32])=[N:9][N:8]([C:5]4[CH:6]=[CH:7][C:2](/[CH:59]=[CH:58]/[C:56]([OH:60])([CH3:57])[CH3:55])=[CH:3][CH:4]=4)[C:16]=3[C:15]=2[CH:17]=1)=[O:30]

Participants

7

Reactant 4

HCID 82572-Methyl-3-buten-2-olHCID 8471TriethylamineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 22291757HCID 22291757, compound

Product 1

HCID 22291506HCID 22291506, compoundYield 21.6%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A 50 mL round bottomed flask with a magnetic stir bar was charged with 1-(4-bromophenyl)-8-[(2-chlorobenzoyl)amino]-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide (987 mg, 1.89 mmol), palladium (II) acetate (44 mg, 0.19 mmol), 1,1′-biphenyl-2-yl[di(tert-butyl)]phosphine (254 mg, 0.822 mmol), and dimethylformamide (20 mL). The resulting solution was sparged with argon for 10 minutes. To the solution was added 2-methyl-3-buten-2-ol (823 mg, 6.07 mmol) and triethylamine (614 mg, 6.07 mmol). The solution was sparged with argon for an additional 2 minutes. The flask was sealed with a rubber septum and heated to 100° C. in an oil bath for 90 minutes. The reaction was allowed to cool to room temperature and water was added. The resulting precipitate was collected and purified by silica gel chromatography (100% hexane to 100% ethyl acetate). The pure fractions were combined, concentrated to dryness, triturated with diethyl ether, and dried under vacuum to give 215 mg of 8-[(2-chlorobenzoyl)amino]-1-{4-[(1E)-3-hydroxy-3-methylbut-1-enyl]phenyl}-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide (0.408 mmol, 21% yield) as a solid. 1H NMR (400 MHz, DMSO-d6) δ 1.29 (s, 6 H), 2.88-2.98 (m, 4 H), 4.76 (s, 1 H), 6.48 (d, 1 H), 6.58 (d, 1 H), 7.23 (d, 1 H), 7.30-7.50 (m, 8 H), 7.53-7.59 (m, 3 H), 10.28 (s, 1 H); MS (ESI+) for C30H27ClN4O3 m/z 527 (M+H)+.

Workup

  1. customThe resulting solution was sparged with argon for 10 minutes
  2. customThe solution was sparged with argon for an additional 2 minutes
  3. customThe flask was sealed with a rubber septum
  4. temperatureto cool to room temperature
  5. additionwater was added
  6. customThe resulting precipitate was collected
  7. custompurified by silica gel chromatography (100% hexane to 100% ethyl acetate)
  8. concentrationconcentrated to dryness
  9. customtriturated with diethyl ether
  10. customdried under vacuum

Sources & evidence

ORD record
ord-db1a1c9194c24afba288da4bf6940f8f
Source dataset
uspto-grants-2005_10
Patent number
US06956052B2

Reaction notes

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