HCID 86716522, compound → HCID 70817844, compound

HRID 1501368Notes

Reaction equation

HRID 1501368 reaction equation
Br[C:2]1[CH:3]=[C:4](/[CH:35]=[CH:36]/[C:37]([O:39][CH3:40])=[O:38])[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(OC(C)(C)C)=O)[CH2:20][CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[N:10]=2)[N:7]=1>[Pd].C(O)C.C1COCC1>[NH2:21][C:17]1([C:14]2[CH:15]=[CH:16][C:11]([C:9]3[N:10]=[C:5]4[C:4]([CH2:35][CH2:36][C:37]([O:39][CH3:40])=[O:38])=[CH:3][CH:2]=[N:7][N:6]4[C:8]=3[C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)=[CH:12][CH:13]=2)[CH2:18][CH2:19][CH2:20]1

Participants

5

Reactant 1

HCID 86716522HCID 86716522, compound

Product 1

HCID 70817844HCID 70817844, compoundYield 1%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalyst2×HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of methyl (2E)-3-[6-bromo-2-(4-{1-[(tert-butoxycarbonyl)amino]cyclobutyl}phenyl)-3-phenylimidazo[1,2-b]pyridazin-8-yl]acrylate that was prepared in a manner analgous to that described for Example 72, Step 1 (0.50 g, 0.83 mmol) and 10% palladium on carbon (0.26 g) in a mixture of ethanol (14 mL) and THF (5 mL) was placed under a hydrogen atmosphere at room temperature for 1 h. The resulting mixture was treated with additional 10% palladium on carbon (0.26 g) and placed under a hydrogen atmosphere for 1 h. Solids were removed by filtration and washed with ethanol (20 mL). The combined organic solutions were treated with 10% palladium on carbon (0.26 g) and placed under a hydrogen atmosphere for 1 h. Solids were removed by filtration and washed with ethanol (20 mL). The combined organic solutions were concentrated under reduced pressure. The resulting material was purified using MPLC (Biotage Isolera; Snap 25 g cartridge, 100% hexane 2.0 min, gradient to 80% hexane/20% EtOAc 1.5 min, gradient to 74% hexane/26% EtOAc 2.5 min, gradient to 70% hexane/30% EtOAc 2.0 min, gradient to 50% hexane/50% EtOAc 3.0 min, 50% hexane/50% EtOAc 6.4 min, gradient to 25% hexane/75% EtOAc 3.5 min, 25% hexane/75% EtOAc 5.3 min gradient to 100% EtOAc 5.3 min, 100% EtOAc 21.2 min). The resulting material was further purified using preparative HPLC (Agilent Prep 1200 equipped with 2× Prep Pump, DLA, MWD, ELSD and Prep FC using an XBrigde C18 5 μm 100×30 mm column; gradient from 100% water with 0.1% HCO2H to 70% water with 0.1% HCO2H/30% MeOH over 1.0 min, gradient to 30% water with 0.1% HCO2H/70% MeOH over 7.0 min, gradient to 100% MeOH over 0.1 min, 100% MeOH 1.9 min) to give methyl 3-{2-[4-(1-aminocyclobutyl)phenyl]-3-phenylimidazo[1,2-b]pyridazin-8-yl}propanoate (0.003 g, 1%):

Workup

  1. customwas prepared in a manner analgous to
  2. waitplaced under a hydrogen atmosphere for 1 h
  3. customSolids were removed by filtration
  4. washwashed with ethanol (20 mL)
  5. additionThe combined organic solutions were treated with 10% palladium on carbon (0.26 g)
  6. waitplaced under a hydrogen atmosphere for 1 h
  7. customSolids were removed by filtration
  8. washwashed with ethanol (20 mL)
  9. concentrationThe combined organic solutions were concentrated under reduced pressure
  10. customThe resulting material was purified
  11. customMPLC (Biotage Isolera; Snap 25 g cartridge, 100% hexane 2.0 min, gradient to 80% hexane/20% EtOAc 1.5 min, gradient to 74% hexane/26% EtOAc 2.5 min, gradient to 70% hexane/30% EtOAc 2.0 min, gradient to 50% hexane/50% EtOAc 3.0 min, 50% hexane/50% EtOAc 6.4 min, gradient to 25% hexane/75% EtOAc 3.5 min, 25% hexane/75% EtOAc 5.3 min gradient to 100% EtOAc 5.3 min, 100% EtOAc 21.2 min)
  12. customThe resulting material was further purified
  13. customequipped with 2× Prep Pump, DLA, MWD, ELSD and Prep FC
  14. waitgradient from 100% water with 0.1% HCO2H to 70% water with 0.1% HCO2H/30% MeOH over 1.0 min
  15. waitgradient to 30% water with 0.1% HCO2H/70% MeOH over 7.0 min
  16. waitgradient to 100% MeOH over 0.1 min

Sources & evidence

ORD record
ord-803fa3a792fd4820b12629c237886ec9
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

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