Chlorosuccinimide → HCID 88857409, compound

HRID 1754147Notes

Reaction equation

HRID 1754147 reaction equation
[Cl:1]N1C(=O)CCC1=O.[NH2:9][C:10]1[C:15]([F:16])=[C:14]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([O:24][CH3:25])[C:18]=2[F:26])[N:13]=[C:12]([C:27]([O:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[O:28])[C:11]=1/[CH:37]=[CH:38]/[Si](C)(C)C>CN(C=O)C.O>[NH2:9][C:10]1[C:15]([F:16])=[C:14]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([O:24][CH3:25])[C:18]=2[F:26])[N:13]=[C:12]([C:27]([O:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[O:28])[C:11]=1/[CH:37]=[CH:38]/[Cl:1]

Participants

5

Reactant 2

HCID 31398ChlorosuccinimideHCID 131733667HCID 131733667, compound

Product 1

HCID 88857409HCID 88857409, compoundYield 22%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

N-Chlorosuccinimide (NCS; 190 mg, 1.4 mmol, 2.0 equiv) was added to a stirred solution of (E)-benzyl 4-amino-6-(4-chloro-2-fluoro-3-methoxyphenyl)-5-fluoro-3-(2-(trimethylsilyl)vinyl)picolinate (350 mg, 0.70 mmol, 1.0 equiv) in DMF (7.0 mL) at 23° C. The homogeneous pale green solution was heated to 50° C. and stirred for 24 h. The cooled reaction mixture was diluted with water (400 mL) and extracted with Et2O (4×100 mL). The combined organic layers were dried (MgSO4), gravity filtered, and concentrated by rotary evaporation. The residue was purified by reverse phase column chromatography (5% acetonitrile to 100% acetonitrile gradient) to afford the desired product, (E)-benzyl 4-amino-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-(2-chlorovinyl)-5-fluoropicolinate as a tan powder (70 mg, 22% yield): mp 133-135° C.; IR (thin film) 3486 (s), 3345 (s), 3215 (w), 3069 (w), 3037 (w), 2953 (w), 1719 (s), 1616 (s) cm−1; 1H NMR (400 MHz, CDCl3) δ 7.47-7.43 (m, 2H), 7.41-7.33 (m, 3H), 7.27 (m, 2H), 6.89 (d, J=14 Hz, 1H), 6.45 (d, J=14 Hz, 1H), 5.37 (s, 2H), 4.62 (br s, 2H), 3.97 (d, J=1 Hz, 3H); ESIMS m/z 465 ([M+H]+).

Workup

  1. customThe cooled reaction mixture
  2. extractionextracted with Et2O (4×100 mL)
  3. dry with materialThe combined organic layers were dried (MgSO4), gravity
  4. filtrationfiltered
  5. concentrationconcentrated by rotary evaporation
  6. customThe residue was purified by reverse phase column chromatography (5% acetonitrile to 100% acetonitrile gradient)

Sources & evidence

ORD record
ord-55ebc78df90e4616a03260a239385bea
Source dataset
uspto-grants-2015_10
Patent number
US09169217B2

Reaction notes

Loading…