tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate → HCID 86710717, compound

HRID 1027290Notes

Reaction equation

HRID 1027290 reaction equation
Br[C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([C:10]2[N:15]=[N:14][C:13]([N:16]([CH3:27])[CH:17]3[CH2:22][C:21]([CH3:24])([CH3:23])[NH:20][C:19]([CH3:26])([CH3:25])[CH2:18]3)=[CH:12][CH:11]=2)=[C:4]([F:28])[CH:3]=1.BrC1C=C(C2C(OC)=CC=CC=2F)N=N[C:31]=1[N:45](C)[CH:46]1CC(C)(C)[NH:49][C:48](C)(C)[CH2:47]1.BrC1C=C(F)C(C2N=NC(N(C)C3CC(C)(C)NC(C)(C)C3)=CC=2)=C(O)C=1.CC1(C)C(C)(C)OB(C2C=NN(C(OC(C)(C)C)=O)C=2)O1>>[F:28][C:4]1[CH:3]=[CH:2][CH:7]=[C:6]([O:8][CH3:9])[C:5]=1[C:10]1[N:15]=[N:14][C:13]([N:16]([CH3:27])[CH:17]2[CH2:22][C:21]([CH3:24])([CH3:23])[NH:20][C:19]([CH3:25])([CH3:26])[CH2:18]2)=[C:12]([C:47]2[CH:48]=[N:49][N:45]([CH3:31])[CH:46]=2)[CH:11]=1

Participants

5

Reactant 4

HCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 86710627HCID 86710627, compoundHCID 86710718HCID 86710718, compoundHCID 136377154HCID 136377154, compound

Product 1

HCID 86710717HCID 86710717, compound

Procedure

Following GENERAL METHOD 1-6 for Suzuki cross-coupling, a mixture of 6-(4-bromo-2-fluoro-6-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine, 4-bromo-6-(2-fluoro-6-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (Intermediate 8-1, Step 2, 0.10 g, 0.22 mmol, total amount of the 2 regioisomers) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (0.14 g, 0.67 mmol) were reacted. The crude product was purified by column chromatography using silica gel and a gradient elution of 1-15% 7 N ammonia in MeOH, in CH2Cl2. An inseparable mixture of the desired product (6-(2-fluoro-6-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6 tetramethylpiperidin-4-yl)pyridazin-3-amine) and 6-(2-fluoro-6-methoxyphenyl)-N-methyl-4-(1-methyl-1H-pyrazol-4-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine was afforded as a colorless solid (80 mg, 80%). [M+H]: 453.4.

Workup

  1. customwere reacted
  2. customThe crude product was purified by column chromatography
  3. washa gradient elution of 1-15% 7 N ammonia in MeOH
  4. additionAn inseparable mixture of the desired product (6-(2-fluoro-6-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6 tetramethylpiperidin-4-yl)pyridazin-3-amine)

Sources & evidence

ORD record
ord-0cc7d7daf5f54a46b94dc64f82587617
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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