Ammonium Chloride → HCID 86716513, compound

HRID 1501341Notes

Reaction equation

HRID 1501341 reaction equation
CON(C)[C:4]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:13]=[CH:14][C:15]3[N:16]([C:18]([C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)=[C:19]([C:21]4[CH:26]=[CH:25][C:24]([C:27]5([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:30][CH2:29][CH2:28]5)=[CH:23][CH:22]=4)[N:20]=3)[N:17]=2)=[CH:8][CH:7]=1)=[O:5].[CH3:46][Mg]Cl.[Cl-].[NH4+]>C1COCC1>[C:4]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:13]=[CH:14][C:15]3[N:16]([C:18]([C:39]4[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=4)=[C:19]([C:21]4[CH:22]=[CH:23][C:24]([C:27]5([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:35])([CH3:36])[CH3:37])[CH2:28][CH2:29][CH2:30]5)=[CH:25][CH:26]=4)[N:20]=3)[N:17]=2)=[CH:8][CH:7]=1)(=[O:5])[CH3:46]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 86716512HCID 86716512, compoundHCID 178418332HCID 178418332, compound2×

Product 1

HCID 86716513HCID 86716513, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl {1-[4-(6-{4-[methoxy(methyl)carbamoyl]phenyl}-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-30 (0.25 g, 0.47 mmol) in THF (10 mL) at 0° C. under an argon atmosphere was added methylmagnesium chloride (3 M in THF, 0.40 mL, 1.19 mmol, 2.5 equiv) portionwise through a septum. The resulting mixture was stirred at 0° C. and at room temperature for 5 h. Additional methylmagnesium chloride (3 M in THF, 0.16 mL, 0.48 mmol, 1.0 equiv) was added and the resulting mixture was stirred for 12 h. The resulting mixture was added to a saturated aqueous ammonium chloride solution (25 mL). The aqueous mixture was extracted with EtOAc (3×25 mL). The combined organic phases were dried (Na2SO4 anh.) and concentrated under reduced pressure. The resulting yellow oil (0.23 g) was purified using MPLC (Biotage Isolera; Snap 10 g cartridge, 100% hexane 2.0 min, gradient to 50% hexane/50% EtOAc 2.0 min, 50% hexane/50% EtOAc 2.0 min, gradient to 100% EtOAc 5.0 min, 100% EtOAc 21.0 min) to give tert-butyl (1-{4-[6-(4-acetylphenyl)-3-phenylimidazo[1,2-b]pyridazin-2-yl]phenyl}cyclobutyl)carbamate (0.053 g, 23%):

Workup

  1. stirringthe resulting mixture was stirred for 12 h
  2. extractionThe aqueous mixture was extracted with EtOAc (3×25 mL)
  3. dry with materialThe combined organic phases were dried (Na2SO4 anh.)
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting yellow oil (0.23 g) was purified
  6. customMPLC (Biotage Isolera; Snap 10 g cartridge, 100% hexane 2.0 min, gradient to 50% hexane/50% EtOAc 2.0 min, 50% hexane/50% EtOAc 2.0 min, gradient to 100% EtOAc 5.0 min, 100% EtOAc 21.0 min)

Sources & evidence

ORD record
ord-29cfcf40f39e40249d1545f72903f415
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

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