Phenylboronic Acid → 5-Benzyl-2-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-3-phenyl-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

HRID 2097419Notes

Reaction equation

HRID 2097419 reaction equation
[CH2:1]([N:8]1[C:13](=[O:14])[C:12]2[C:15](I)=[C:16]([C:26]3[CH:31]=[CH:30][C:29]([O:32][CH:33]([F:35])[F:34])=[C:28]([O:36][CH2:37][CH:38]4[CH2:40][CH2:39]4)[CH:27]=3)[N:17]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:11]=2[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.BrC1N(COCC[Si](C)(C)C)C2C=NNC(=O)C=2C=1.[C:61]1(B(O)O)[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCCC1>[CH2:1]([N:8]1[C:13](=[O:14])[C:12]2[C:15]([C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=3)=[C:16]([C:26]3[CH:31]=[CH:30][C:29]([O:32][CH:33]([F:35])[F:34])=[C:28]([O:36][CH2:37][CH:38]4[CH2:40][CH2:39]4)[CH:27]=3)[N:17]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:11]=2[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 66827Phenylboronic AcidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 666025865-Benzyl-2-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-3-iodo-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-oneHCID 666026402-Bromo-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

Product 1

HCID 666027755-Benzyl-2-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-3-phenyl-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-oneYield 93%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Reaction and post treatment were carried out in the same manner as in Example 1-(a) except for using 383 mg (0.552 mmol) of 5-benzyl-2-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-3-iodo-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in Example 38-(c) in place of 2-bromo-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, using 84 mg (0.69 mmol) of phenylboronic acid in place of 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane, and using 55 μl of tetrahydrofuran solution containing 100 mM palladium complex prepared previously from 231 mg (1.03 mmol) of palladium acetate and 846 mg of 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl in place of tetrakis(triphenylphosphine)palladium, whereby 330 mg of the title compound was obtained as a pale brownish foam. (Yield: 93%)

Workup

  1. customReaction and post treatment
  2. additioncontaining 100 mM palladium complex

Sources & evidence

ORD record
ord-45dea10bc132492092cc1efb9a1208d7
Source dataset
uspto-grants-2013_05
Patent number
US08450319B2

Reaction notes

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