Diisopropylethylamine → Tert-butyl {1-[4-(6-methyl-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]-cyclobutyl}carbamate

HRID 1501320Notes

Reaction equation

HRID 1501320 reaction equation
Br[CH:2]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:14][CH2:13][CH2:12]2)=[CH:7][CH:6]=1)=O.[CH3:29][C:30]1[N:35]=[N:34][C:33]([NH2:36])=[CH:32][CH:31]=1.C(N(CC)C(C)C)(C)C>C(O)(C)C>[CH3:29][C:30]1[CH:31]=[CH:32][C:33]2[N:34]([C:2]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[C:3]([C:5]3[CH:10]=[CH:9][C:8]([C:11]4([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:14][CH2:13][CH2:12]4)=[CH:7][CH:6]=3)[N:36]=2)[N:35]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 877126-Methylpyridazin-3-amineHCID 86691038tert-Butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamate

Product 1

HCID 86716494Tert-butyl {1-[4-(6-methyl-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]-cyclobutyl}carbamate

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of crude tert-butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamate that was prepared in a manner analgous to that described for Intermediate Example Int-1-A (1.00 g, ˜80% purity, 1.87 mmol, 1.0 eq), 6-methylpyridazin-3-amine (CAS-Nr. 18591-82-7, 0.245 g, 2.24 mmol, 1.2 eq), N,N-diisopropylethylamine (0.33 mL, 1.87 mmol, 1.0 eq) and activated 3 Å molecular sieves in isopropanol (5.7 mL) was heated for 7 hours under reflux. On cooling, the mixture was partitioned between DCM and water, stirred vigorously and filtered through a silicone coated filter paper. The filtrate was concentrated in vacuo. UPLC analysis of the crude product indicated a purity of >90%. The crude product was used in the next step without further purification.

Workup

  1. customwas prepared in a manner analgous to
  2. temperaturewas heated for 7 hours
  3. temperatureunder reflux
  4. temperatureOn cooling
  5. customthe mixture was partitioned between DCM and water
  6. filtrationfiltered through a silicone coated filter paper
  7. concentrationThe filtrate was concentrated in vacuo
  8. customThe crude product was used in the next step without further purification

Sources & evidence

ORD record
ord-dfadddfe6cfa46d58ea928ec65bb67c1
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

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