1,2-Dichloroethane → HCID 77978833, compound

HRID 2283502Notes

Reaction equation

HRID 2283502 reaction equation
[OH:1][C:2]1([C:13]2[N:18]=[CH:17][C:16]([C:19]3[CH:24]=[C:23]([CH3:25])[CH:22]=[C:21]([NH:26][C:27]4[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[CH:29][N:28]=4)[N:20]=3)=[CH:15][CH:14]=2)[CH2:7][CH2:6][CH:5]([C:8]([OH:10])=O)[C:4]([CH3:12])([CH3:11])[CH2:3]1.C(Cl)CCl.C1C=CC2N(O)N=[N:47]C=2C=1.CCN(C(C)C)C(C)C.[Cl-].[NH4+]>CN(C=O)C.O>[OH:1][C:2]1([C:13]2[N:18]=[CH:17][C:16]([C:19]3[CH:24]=[C:23]([CH3:25])[CH:22]=[C:21]([NH:26][C:27]4[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[CH:29][N:28]=4)[N:20]=3)=[CH:15][CH:14]=2)[CH2:7][CH2:6][CH:5]([C:8]([NH2:47])=[O:10])[C:4]([CH3:12])([CH3:11])[CH2:3]1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 70982668HCID 70982668, compound

Product 1

HCID 77978833HCID 77978833, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a flask containing (1S,4S or 1R,4R)-4-hydroxy-2,2-dimethyl-4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}-2,3′-bipyridin-6′-yl)cyclohexanecarboxylic acid (267 mg, 0.366 mmol), EDC (141 mg, 0.733 mmol), HOBt (112 mg, 0.733 mmol) and DIEA (0.320 mL, 1.832 mmol) in DMF (3.66 mL) was added ammonium chloride (59 mg, 1.099 mmol). The solution was stirred at room temperature for 16 hours. Water was added, and the mixture extracted with ethyl acetate (3×). The organic layers were combined, dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (6% methanol:dichloromethane) to afford (1S,4S or 1R,4R)-4-hydroxy-2,2-dimethyl-4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}-2,3′-bipyridin-6′-yl)cyclohexanecarboxamide as a white solid. MS ESI calcd. for C26H29F3N5O2 [M+H]+ 500. found 500. 1H NMR (600 MHz, DMSO-d6) δ 10.19 (s, 1H), 9.10 (d, J=1.7 Hz, 1H), 8.54 (s, 1H), 8.47 (d, J=5.2 Hz, 1H), 8.33 (dd, J=8.4, 2.3 Hz, 1H), 7.65 (d, J=8.4 Hz, 1H), 7.43 (s, 1H), 7.30 (s, 1H), 7.17 (d, J=5.2 Hz, 1H), 7.16 (s, 1H), 6.54 (s, 1H), 4.99 (s, 1H), 2.63-2.57 (m, 1H), 2.36 (d, J=13.6 Hz, 1H), 2.34 (s, 3H), 2.10 (t, J=5.1 Hz, 1H), 1.96-1.90 (m; 1H), 1.75-1.65 (m, 1H), 1.41-1.35 (m, 1H), 1.32 (d, J=13.4 Hz, 1H), 1.09 (s, 3H), 0.61 (s, 3H). rhSyk IC50=23 nM.

Workup

  1. extractionthe mixture extracted with ethyl acetate (3×)
  2. dry with materialdried with magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by chromatography on silica gel (6% methanol:dichloromethane)

Sources & evidence

ORD record
ord-eea9d928cf9c4591a046ba99a214976c
Source dataset
uspto-grants-2015_09
Patent number
US09145391B2

Reaction notes

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