(Bis(2-methoxyethyl)amino)sulfur trifluoride → 8-(1-Ethyl-1-fluoro-propyl)-2,6-dimethyl-3-[3-methyl-5-(6-methyl-pyridin-2-yl)-thiophen-2-yl]-imidazo[1,2-b]pyridazine

HRID 1432642Notes

Reaction equation

HRID 1432642 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]2[C:9]([C:10](O)([CH2:13][CH3:14])[CH2:11][CH3:12])=[CH:8][C:7]([CH3:16])=[N:6][N:5]2[C:17]=1[C:18]1[S:19][C:20]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=2)=[CH:21][C:22]=1[CH3:23].COCCN(S(F)(F)[F:41])CCOC>C(Cl)Cl>[CH2:11]([C:10]([C:9]1[C:4]2[N:5]([C:17]([C:18]3[S:19][C:20]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=4)=[CH:21][C:22]=3[CH3:23])=[C:2]([CH3:1])[N:3]=2)[N:6]=[C:7]([CH3:16])[CH:8]=1)([F:41])[CH2:13][CH3:14])[CH3:12]

Participants

4

Reactant 2

HCID 2734690(Bis(2-methoxyethyl)amino)sulfur trifluorideHCID 688404123-{2,6-Dimethyl-3-[3-methyl-5-(6-methyl-pyridin-2-yl)-thiophen-2-yl]-imidazo[1,2-b]pyridazin-8-yl}-pentan-3-ol

Product 1

HCID 579330738-(1-Ethyl-1-fluoro-propyl)-2,6-dimethyl-3-[3-methyl-5-(6-methyl-pyridin-2-yl)-thiophen-2-yl]-imidazo[1,2-b]pyridazineYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a −78° C. solution of 3-{2,6-dimethyl-3-[3-methyl-5-(6-methyl-pyridin-2-yl)-thiophen-2-yl]-imidazo[1,2-b]pyridazin-8-yl}-pentan-3-ol (0.23 g, 0.55 mmol) and CH2Cl2 (3 mL) is added a solution of [bis(2-methoxyethyl)amino]sulfur triflouride (0.14 g, 0.60 mmol) and CH2Cl2 (2 mL). The solution is warmed to ambient temperature and stirred overnight. The solution is washed with sat. NaHCO3 (5 mL) and concentrated. The reside is purified by ISCO column chromatography (15%-20% EtOAc/hexane gradient) furnish the title compound (0.13 g, 0.31 mmol, 57%). 1H NMR (CDCl3) δ 0.80 (t, J=7.5 Hz, 6H), 2.14 (s, 3H), 2.16-2.31 (m, 2H), 2.46 (s, 3H), 2.54 (s, 3H), 2.56 (s, 3H), 2.59-2.70 (m, 2H), 6.98 (s, 1H), 7.00 (d, J=7.6 Hz, 1H), 7.45 (d, J=7.8 Hz, 1H), 7.52 (s, 1H), 7.56 (dd, J=7.8, 7.6 Hz, 1H). LC/MS (m/z): calcd. for C24H27FN4S (M+H)+: 423.2; found: 423.4.

Workup

  1. washThe solution is washed with sat. NaHCO3 (5 mL)
  2. concentrationconcentrated
  3. customThe reside is purified by ISCO column chromatography (15%-20% EtOAc/hexane gradient)

Sources & evidence

ORD record
ord-0564c8f831db4627a94dfd3cfee498a0
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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