Ammonium Chloride → (E)-tert-Butyl 5-(8-morpholino-2-(2-(5,6,7,8-tetrahydroquinolin-2-yl)vinyl)imidazo[1,2-b]pyridazin-3-yl)picolinate

HRID 718676Notes

Reaction equation

HRID 718676 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11]P(=O)(OCC)OCC.[Li]CCCC.[CH:25]([C:27]1[N:28]=[C:29]2[C:34]([N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[CH:33][CH:32]=[N:31][N:30]2[C:41]=1[C:42]1[CH:43]=[CH:44][C:45]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])=[N:46][CH:47]=1)=O.[NH4+].[Cl-]>C1COCC1.O>[O:38]1[CH2:39][CH2:40][N:35]([C:34]2[C:29]3[N:30]([C:41]([C:42]4[CH:43]=[CH:44][C:45]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])=[N:46][CH:47]=4)=[C:27](/[CH:25]=[CH:11]/[C:2]4[CH:3]=[CH:4][C:5]5[CH2:6][CH2:7][CH2:8][CH2:9][C:10]=5[N:1]=4)[N:28]=3)[N:31]=[CH:32][CH:33]=2)[CH2:36][CH2:37]1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 11011347Diethyl 2-quinolinylmethylphosphonateHCID 117732517tert-Butyl 5-(2-formyl-8-morpholinoimidazo[1,2-b]pyridazin-3-yl)picolinateHCID 178418339Butyllithium

Product 1

HCID 117732519(E)-tert-Butyl 5-(8-morpholino-2-(2-(5,6,7,8-tetrahydroquinolin-2-yl)vinyl)imidazo[1,2-b]pyridazin-3-yl)picolinate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of compound 58a (218 mg, 0.771 mmol) in 3 mL of THF at rt was added n-BuLi (482 μL, 0.771 mmol, 1.6M in hexane) dropwise. After stirring at rt for 15 min, the mixture was added slowly to a suspension of compound 61a (263 mg, 0.642 mmol) in 5 mL of THF. The resulting mixture was stirred at rt for 1 h then 2 mL of saturated NH4Cl was added. The mixture was diluted with 10 mL of water, and the mixture was extracted with EtOAc (2×20 mL). The combined organic layers were washed with brine (15 mL) and dried with Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography on silica gel (0:1-1:4 EtOAc-DCM) to afford compound 61b as a pale yellow solid. 1H-NMR (CDCl3; 400 MHz) δ 9.07 (d, J=2.0 Hz, 1H), 8.25-8.31 (m, 1H), 8.17-8.25 (m, 1H), 7.98 (d, J=5.6 Hz, 1H), 7.77 (d, J=15.6 Hz, 1H), 7.53 (d, J=15.7 Hz, 1H), 7.29-7.37 (m, 1H), 7.23-7.29 (m, 1H), 6.13 (d, J=5.9 Hz, 1H), 4.02-4.11 (m, 4H), 3.91-4.02 (m, 4H), 2.88-2.98 (m, 2H), 2.69-2.83 (m, 2H), 1.86-1.96 (m, 2H), 1.77-1.86 (m, 2H), 1.68 (s, 9H). Mass spectrum (ESI, m/z): Calcd. for C31H34N6O3, 539.3 (M+H). found 539.5.

Workup

  1. stirringThe resulting mixture was stirred at rt for 1 h
  2. extractionthe mixture was extracted with EtOAc (2×20 mL)
  3. washThe combined organic layers were washed with brine (15 mL)
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography on silica gel (0:1-1:4 EtOAc-DCM)

Sources & evidence

ORD record
ord-b656f2a0772c4e4db611a7ac8d5efa33
Source dataset
uspto-grants-2015_11
Patent number
US09193736B2

Reaction notes

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