Diisopropylethylamine → (S)-6-(1-(1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-ylamino)pyridazine-3-carbonitrile

HRID 407998Notes

Reaction equation

HRID 407998 reaction equation
[NH2:1][C@H:2]1[CH2:6][CH2:5][N:4]([CH:7]2[CH2:12][CH2:11][N:10]([C:13]3[C:18]([Cl:19])=[CH:17][C:16]([C:20]([F:23])([F:22])[F:21])=[CH:15][N:14]=3)[CH2:9][CH2:8]2)[C:3]1=[O:24].C(N(C(C)C)C(C)C)C.Cl[C:35]1[N:40]=[N:39][C:38]([C:41]#[N:42])=[CH:37][CH:36]=1>CN(C=O)C.CCOC(C)=O>[Cl:19][C:18]1[C:13]([N:10]2[CH2:11][CH2:12][CH:7]([N:4]3[CH2:5][CH2:6][C@H:2]([NH:1][C:35]4[N:40]=[N:39][C:38]([C:41]#[N:42])=[CH:37][CH:36]=4)[C:3]3=[O:24])[CH2:8][CH2:9]2)=[N:14][CH:15]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:17]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 133828716-Chloropyridazine-3-carbonitrileHCID 67469689(S)-3-amino-1-(1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)pyrrolidin-2-one

Product 1

HCID 54670892(S)-6-(1-(1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-ylamino)pyridazine-3-carbonitrileYield 14.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of (S)-3-amino-1-(1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)pyrrolidin-2-one (0.15 g, 0.41 mmol) in DMF (10 mL) was added N-ethyl-N-isopropylpropan-2-amine (0.160 g, 1.24 mmol) and 6-chloropyridazine-3-carbonitrile (0.173 g, 1.24 mmol) and the reaction was heated to 90° C. overnight. The reaction was diluted with EtOAc (150 mL) and washed with water (100 mL), and brine (10 mL), dried over MgSO4, filtered and concentrated under vacuum. The material was purified on silica, using 1:1 EtOAc:DCM as eluent to yield a solid, which was further triturated with diethyl ether to yield (S)-6-(1-(1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-ylamino)pyridazine-3-carbonitrile (0.028 g, 0.060 mmol, 14% yield). Mass spectrum (apci) m/z=466.0, 467.9 (M+H).

Workup

  1. washwashed with water (100 mL), and brine (10 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe material was purified on silica
  6. customDCM as eluent to yield a solid, which
  7. customwas further triturated with diethyl ether

Sources & evidence

ORD record
ord-4f49a5aec992422eb4841ff1f1d5475d
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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