Dimethylformamide → HCID 86603603, compound

HRID 1437454Notes

Reaction equation

HRID 1437454 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:10][CH2:11][NH:12][CH:13]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=2)[CH:14]=1.[CH3:23]N(C=O)C.[C:28]([O:32][C:33]([NH:35][C@H:36]([C:40]([OH:42])=O)[CH:37]([CH3:39])[CH3:38])=[O:34])([CH3:31])([CH3:30])[CH3:29].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:10][CH2:11][N:12]([CH2:23][C:40](=[O:42])[C@@H:36]([NH:35][C:33](=[O:34])[O:32][C:28]([CH3:29])([CH3:30])[CH3:31])[CH:37]([CH3:38])[CH3:39])[CH:13]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=2)[CH:14]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 83693Boc-L-ValineHCID 2724699PyBOPHCID 57941176HCID 57941176, compound

Product 1

HCID 86603603HCID 86603603, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
23 °C

Procedure

To a stir bar equipped flask containing 4-(2,5-difluorophenyl)-6-(3-methoxyphenyl)-1,2,3,6-tetrahydropyridne (1-5, 0.06 g, 0.19 mmol) under nitrogen was added DMF (10 mL) successively followed by N-(tert-butoxycarbonyl)-L-valine (0.08 g, 0.39 mmol), TEA (0.14 mL, 0.99 mmol), and PyBop (benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate) (0.20 g, 0.39 mmol). The resulting solution stirred at 23° C. over 72 h. Upon completion, the reaction was diluted with dichloromethane (20 mL) and washed with aqueous sodium chloride (3×50 mL). The organics were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash column chromatography (SiO2, 0-30% EtOAc/hexanes gradient) to give tert-butyl (1S)-3-[4-(2,5-difluorophenyl)-6-(3-methoxyphenyl)-3,6-dihydropyridin-1(2H)-yl]-1-isopropyl-2-oxopropylcarbamate (2-1). MS 445.0 found, 445.5 required (MH+−C(CH)3).

Workup

  1. customTo a stir bar equipped flask
  2. washwashed with aqueous sodium chloride (3×50 mL)
  3. dry with materialThe organics were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude residue was purified by flash column chromatography (SiO2, 0-30% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-a07dba80ed2347c9bad06becfda436db
Source dataset
uspto-grants-2009_11
Patent number
US07622489B2

Reaction notes

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