Water → tert-Butyl 2-(tert-butoxycarbonyl(5-(8-morpholino-2-(quinolin-2-ylethynyl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)amino)acetate

HRID 718621Notes

Reaction equation

HRID 718621 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]3[N:9]([C:13]([C:28]4[CH:29]=[CH:30][C:31]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[N:32][CH:33]=4)=[C:14]([C:16]#[C:17][C:18]4[CH:27]=[CH:26][C:25]5[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=5)[N:19]=4)[N:15]=3)[N:10]=[CH:11][CH:12]=2)[CH2:3][CH2:2]1.[H-].[Na+].[C:44]([O:48][C:49]([CH2:51]C(OC(C)(C)C)=O)=[O:50])([CH3:47])([CH3:46])[CH3:45].O>CN(C=O)C>[C:37]([O:36][C:35]([N:34]([C:31]1[CH:30]=[CH:29][C:28]([C:13]2[N:9]3[N:10]=[CH:11][CH:12]=[C:7]([N:4]4[CH2:5][CH2:6][O:1][CH2:2][CH2:3]4)[C:8]3=[N:15][C:14]=2[C:16]#[C:17][C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:19]=2)=[CH:33][N:32]=1)[CH2:51][C:49]([O:48][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:50])=[O:41])([CH3:38])([CH3:40])[CH3:39]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 68324Di-tert-butyl malonateHCID 117732491tert-Butyl 5-(8-morpholino-2-(2-(quinolin-2-yl)ethynyl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-ylcarbamate

Product 1

HCID 117732492tert-Butyl 2-(tert-butoxycarbonyl(5-(8-morpholino-2-(quinolin-2-ylethynyl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)amino)acetate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of compound 38a (1.0 g, 1.7 mmol) in DMF (20 mL), was added sodium hydride (60%, 0.11 g, 2.7 mmol) in portions at 0° C. The resulting mixture was stirred at rt for 30 min, and treated with tert-butyl 2-(tert-butoxycarbonyl)acetate (0.53 g, 2.7 mmol). The resulting mixture was stirred at rt for 4 h, and treated with water (100 mL). The solids formed were collected by filtration, washed with Et2O (2×50 mL), and further purified by flash column chromatography on silica gel (ethyl acetate/petroleum ether (2:1)) to obtain compound 38b as a yellow solid. Mass Spectrum (LCMS, ESI pos.): Calcd. for C37H39N7O5: 662.3 (M+H). found: 662.2.

Workup

  1. stirringThe resulting mixture was stirred at rt for 4 h
  2. customThe solids formed
  3. filtrationwere collected by filtration
  4. washwashed with Et2O (2×50 mL)
  5. customfurther purified by flash column chromatography on silica gel (ethyl acetate/petroleum ether (2:1))

Sources & evidence

ORD record
ord-1c42f1439ce448c9ad59b1ca5a1a9ec1
Source dataset
uspto-grants-2015_11
Patent number
US09193736B2

Reaction notes

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