1,2-Dichloroethane → MK-3697

HRID 2047605Notes

Reaction equation

HRID 2047605 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[C:12]([C:14]([O-:16])=O)[C:11]([C:17]3[S:18][CH:19]=[CH:20][N:21]=3)=[CH:10][N:9]=2)[CH:5]=[N:6][CH:7]=1.[K+].[CH3:23][O:24][C:25]1[C:30]([O:31][CH3:32])=[CH:29][CH:28]=[C:27]([CH2:33][NH2:34])[N:26]=1.C(Cl)CCl.ON1C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH3:32][O:31][C:30]1[CH:29]=[CH:28][C:27]([CH2:33][NH:34][C:14]([C:12]2[C:11]([C:17]3[S:18][CH:19]=[CH:20][N:21]=3)=[CH:10][N:9]=[C:8]([C:4]3[CH:5]=[N:6][CH:7]=[C:2]([CH3:1])[CH:3]=3)[CH:13]=2)=[O:16])=[N:26][C:25]=1[O:24][CH3:23]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 574847121-(5,6-Dimethoxypyridin-2-yl)methanamineHCID 67333359Potassium 5'-methyl-5-(thiazol-2-yl)-[2,3'-bipyridine]-4-carboxylate

Product 1

HCID 46190695MK-3697Yield 75%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

Potassium 5′-methyl-5-(1,3-thiazol-2-yl)-2,3′-bipyridine-4-carboxylate (7-4, 980 mg, 2.9 mmol, 1 equiv), 1-(5,6-dimethoxypyridin-2-yl)methanamine (3-6, 490 mg, 2.9 mmol, 1 equiv), EDC (670 mg, 3.5 mmol, 1.2 equiv), 1-hydroxy-7-azabenzotriazole (480 mg, 3.5 mmol, 1.2 equiv) and diisopropylethylamine (2.0 mL, 12 mmol, 4 equiv) were suspended in DMF (14.6 mL) and the reaction mixture was heated for 2 hours at 65° C. The reaction mixture was then partitioned between DCM (50 mL) and water (50 mL). The layers were separated and the organic layer was dried over MgSO4 and concentrated. The residue was purified by normal phase column chromatography (0-20% MeOH in EtOAc) to afford a white solid that was recrystallized from chloroform/hexanes to give the title compound (7-5) as a crystalline solid (970 mg, 75% yield). 1H NMR (CDCl3, 300 MHz) δ 9.08 (s, 2H), 8.53 (s, 1H), 8.22 (s, 1H), 8.11 (s, 1H), 7.81 (dd, J=3.1 and 1.1 Hz, 1H), 7.78 (t, J=4.8 Hz, 1H), 7.43 (dd, J=3.3 and 1.1 Hz, 1H), 7.02 (d, J=7.9 Hz, 1H), 6.85 (d, J=7.7 Hz, 1H), 4.58 (d, J=5.3 Hz, 2H), 3.91 (s, 3H), 3.88 (s, 3H), 2.45 (s, 3H). HRMS (M+H)C23H21N5O3S calc'd 448.1438. found 448.1443

Workup

  1. customThe reaction mixture was then partitioned between DCM (50 mL) and water (50 mL)
  2. customThe layers were separated
  3. dry with materialthe organic layer was dried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified by normal phase column chromatography (0-20% MeOH in EtOAc)
  6. customto afford a white solid
  7. customthat was recrystallized from chloroform/hexanes

Sources & evidence

ORD record
ord-9c108b149db84d1da28bb06c99634fc7
Source dataset
uspto-grants-2013_11
Patent number
US08592457B2

Reaction notes

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