1-Butanol → HCID 70818073, compound

HRID 1501370Notes

Reaction equation

HRID 1501370 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([O:35][CH2:36][CH3:37])[C:7]2[N:8]([C:10]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([C:19]4([NH:23]C(=O)OCC)[CH2:22][CH2:21][CH2:20]4)=[CH:15][CH:14]=3)[N:12]=2)[N:9]=1)[CH3:2].[OH-].[K+].[CH2:40](O)[CH2:41]CC>>[CH2:36]([O:35][C:6]1[C:7]2[N:8]([C:10]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[C:11]([C:13]3[CH:14]=[CH:15][C:16]([C:19]4([NH2:23])[CH2:20][CH2:21][CH2:22]4)=[CH:17][CH:18]=3)[N:12]=2)[N:9]=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=1)[CH2:37][CH2:40][CH3:41]

Participants

4

Reactant 3

HCID 2631-ButanolHCID 14797Potassium HydroxideHCID 86716523HCID 86716523, compound

Product 1

HCID 70818073HCID 70818073, compoundYield 9%

Procedure

A mixture of ethyl {1-[4-(6,8-diethoxy-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]cyclobutyl}carbamate (0.12 g, 0.24 mmol) and potassium hydroxide (powder, 0.077 g, 1.17 mmol, 5.0 equiv) in n-butanol (2.5 mL) was heated at the reflux temperature for 24 h. The resulting mixture was cooled to room temperature and separated between a 4:1 DCM/isopropanol solution (50 mL) and water 50 mL). The organic phase was washed with a saturated aqueous NaCl solution (25 mL), dried (Na2SO4 anh.) and concentrated under reduced pressure. The resulting material was purified using MPLC (Biotage Isolera; SNAP 10 g cartridge: 100% DCM 4.0 min., gradient to 95% DCM/5% MeOH 1 min., 95% DCM/5% MeOH 3.5 min., gradient to 90% DCM/10% MeOH 1 min., 90% DCM/10% MeOH 3.5 min., gradient to 80% DCM/20% MeOH 6 min., 80% DCM/20% MeOH 4.7 min.) to give 1-[4-(8-butoxy-6-ethoxy-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]cyclobutanamine (0.013 g, 9%):

Workup

  1. temperaturewas heated at the reflux temperature for 24 h
  2. customseparated between a 4:1 DCM/isopropanol solution (50 mL) and water 50 mL)
  3. washThe organic phase was washed with a saturated aqueous NaCl solution (25 mL)
  4. dry with materialdried (Na2SO4 anh.)
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting material was purified
  7. customMPLC (Biotage Isolera; SNAP 10 g cartridge: 100% DCM 4.0 min., gradient to 95% DCM/5% MeOH 1 min., 95% DCM/5% MeOH 3.5 min., gradient to 90% DCM/10% MeOH 1 min., 90% DCM/10% MeOH 3.5 min., gradient to 80% DCM/20% MeOH 6 min., 80% DCM/20% MeOH 4.7 min.)

Sources & evidence

ORD record
ord-826fef4cfe504e7b8dd907a180b2fadc
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

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