Tetrahydrofuran → (4-{4-[6-(6-Trifluoromethyl-pyridin-3-ylamino)-pyridazin-3-yl]-phenyl}-cyclohexyl)-acetonitrile

HRID 1404270Notes

Reaction equation

HRID 1404270 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]2[N:15]=[N:14][C:13]([C:16]3[CH:21]=[CH:20][C:19]([CH:22]4[CH2:27][CH2:26][CH:25]([CH2:28][C:29]([NH2:31])=O)[CH2:24][CH2:23]4)=[CH:18][CH:17]=3)=[CH:12][CH:11]=2)=[CH:5][CH:4]=1.C1COCC1.FC(F)(F)C(OC(=O)C(F)(F)F)=O>C(N(CC)CC)C>[F:33][C:2]([F:1])([F:32])[C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]2[N:15]=[N:14][C:13]([C:16]3[CH:21]=[CH:20][C:19]([CH:22]4[CH2:23][CH2:24][CH:25]([CH2:28][C:29]#[N:31])[CH2:26][CH2:27]4)=[CH:18][CH:17]=3)=[CH:12][CH:11]=2)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 9845Trifluoroacetic anhydrideHCID 666159412-(4-{4-[6-(6-Trifluoromethyl-pyridin-3-ylamino)-pyridazin-3-yl]-phenyl}-cyclohexyl)-acetamide

Product 1

HCID 66615964(4-{4-[6-(6-Trifluoromethyl-pyridin-3-ylamino)-pyridazin-3-yl]-phenyl}-cyclohexyl)-acetonitrile

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

To a mixture of 2-(4-{4-[6-(6-Trifluoromethyl-pyridin-3-ylamino)-pyridazin-3-yl]-phenyl}-cyclohexyl)-acetamide (0.18 g, 0.41 mmol, 1.0 equiv) in 3 Ml THF was added trifluoroacetic anhydride (0.068 Ml, 0.49 mmol, 1.2 equiv) followed by triethylamine (0.12 Ml, 0.90 mmol, 2.2 equiv). The reaction was stirred at ambient temperature overnight, and then concentrated in vacuo. Purification by silica gel chromatography (10-50% EtOAc in hexanes) afforded the title compound: 1H NMR (400 MHz, DMSO-d6) δ ppm 1.39-1.50 (m, J=12.82, 12.54, 12.54, 3.54 Hz, 2 H) 1.69-1.80 (m, J=12.88, 12.69, 12.69, 3.41 Hz, 2 H) 1.86-1.97 (m, J=11.91, 11.91, 6.06, 5.87, 2.91 Hz, 1 H) 2.09 (d, J=15.92 Hz, 1 H) 2.09 (dd, J=5.94, 3.66 Hz, 3 H) 2.76 (t, J=3.03 Hz, 1 H) 7.53 (d, J=9.35 Hz, 1 H) 7.59 (d, J=8.34 Hz, 2 H) 8.08 (d, J=8.59 Hz, 1 H) 8.20 (d, J=8.34 Hz, 2 H) 8.30 (d, J=9.35 Hz, 1 H) 8.91 (dd, J=8.59, 2.27 Hz, 1H) 9.16 (d, J=2.53 Hz, 1 H) 10.25 (s, 1 H); (M+H)+ 438.3.

Workup

  1. concentrationconcentrated in vacuo
  2. customPurification by silica gel chromatography (10-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-3cde09deff0245acaa5cb9e9be242acb
Source dataset
uspto-grants-2014_12
Patent number
US08912208B2

Reaction notes

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