Ethanol → HCID 70817736, compound

HRID 1501371Notes

Reaction equation

HRID 1501371 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([C:17]4([NH:21]C(=O)OC(C)(C)C)[CH2:20][CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[N:10]=2)[N:7]=1.[OH-].[K+].[CH2:37]([OH:39])[CH3:38]>>[CH2:37]([O:39][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([C:17]4([NH2:21])[CH2:18][CH2:19][CH2:20]4)=[CH:13][CH:12]=3)[N:10]=2)[N:7]=1)[CH3:38]

Participants

4

Reactant 3

HCID 702EthanolHCID 14797Potassium HydroxideHCID 86716521HCID 86716521, compound

Product 1

HCID 70817736HCID 70817736, compoundYield 42%

Procedure

A mixture of tert-butyl {1-[4-(6-chloro-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]cyclobutyl}carbamate that was prepared in a manner analgous to that described for Intermediate Example Int-6.2 (0.050 g, 0.11 mmol) and potassium hydroxide (powder, 0.050 g, 0.89 mmol, 8.5 equiv) in ethanol (0.8 mL) was irradiated in a microwave apparatus at 120° C. for 120 min. The resulting mixture was added to ice water (10 mL). The aqueous mixture was extracted with a 4:1 DCM/isopropanol solution (4×10 mL). The combined organic phases were 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-(6-ethoxy-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]cyclobutanamine (0.017 g, 42%):

Workup

  1. customwas prepared in a manner analgous to
  2. customwas irradiated in a microwave apparatus at 120° C. for 120 min
  3. extractionThe aqueous mixture was extracted with a 4:1 DCM/isopropanol solution (4×10 mL)
  4. dry with materialThe combined organic phases were dried (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-60d0d444f2ee4215828b8eb33ba9883a
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

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