Lithium Chloride → HCID 117642571, compound

HRID 1507760Notes

Reaction equation

HRID 1507760 reaction equation
[Cl-].[Li+].[CH2:3]([O:10][C:11]1[C:15]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:14](I)[N:13]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[C:12]=1[C:33]([N:35]([CH3:37])[CH3:36])=[O:34])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(OC1C(OCC2C=CC=CC=2)=CN(C2C=CC(OC)=CC=2)C=1C(N(C)C)=O)C1C=CC=CC=1.C([Mg]Cl)(C)C.[CH3:77][P:78](Cl)([CH3:80])=[O:79]>C1COCC1>[CH2:3]([O:10][C:11]1[C:15]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:14]([P:78]([CH3:80])([CH3:77])=[O:79])[N:13]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[C:12]=1[C:33]([N:35]([CH3:37])[CH3:36])=[O:34])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

7

Reactant 5

HCID 433294Lithium Chloride2×HCID 517954Dimethylphosphinic chlorideHCID 89610465HCID 89610465, compoundHCID 117642619HCID 117642619, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 117642571HCID 117642571, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

lithium chloride complex (1.3 M in THF, 315 μL, 0.410 mmol) was added dropwise to a stirred solution of 3,4-bis(benzyloxy)-5-iodo-1-(4-methoxyphenyl)-N,N-dimethyl-1H-pyrrole-2-carboxamide (65) [prepared using the same procedure as Example S step (i) using (9) as starting material] (211 mg, 0.36 mmol) in THF (1.2 mL) at 0° C., the reaction mixture was allowed to stir for 15 min and isopropylmagnesium chloride. lithium chloride complex (1.3 M in THF, 100 μL, 0.13 mmol) was added, and the reaction mixture was allowed to stir for a further 15 min. A solution of dimethylphosphinic chloride (61 mg, 0.54 mmol) in THF (0.6 mL) was added and the reaction allowed to warm to RT and stirred for a further 16 h. The reaction mixture was quenched with 5% AcOH in MeOH (5 mL) and the volatiles removed in vacuo. The residue was purified by silica gel chromatography (12 g, 0-5% MeOH in DCM) to afford a crude residue. The crude residue was further purified by preparative HPLC (Waters, Acidic (0.1% Formic acid), Waters X-Select Prep-C18, 5 μm, 19×50 mm column, 30-60% MeCN in water) to afford 3,4-bis(benzyloxy)-5-(dimethylphosphoryl)-1-(4-methoxyphenyl)-N,N-dimethyl-1H-pyrrole-2-carboxamide (66) (29 mg, 15%) as a colourless gum: m/z 533 (M+H)+ (ES+). 1H NMR (400 MHz, CDCl3) δ: 7.44-7.28 (m, 12H), 6.92-6.87 (m, 2H), 5.22 (s, 2H), 5.05 (s, 2H), 3.82 (s, 3H), 2.76 (s, 3H), 2.63 (s, 3H), 1.41 (br d, J=13 Hz, 6H).

Workup

  1. customprepared
  2. customat 0° C.
  3. stirringto stir for a further 15 min
  4. stirringstirred for a further 16 h
  5. customThe reaction mixture was quenched with 5% AcOH in MeOH (5 mL)
  6. customthe volatiles removed in vacuo
  7. customThe residue was purified by silica gel chromatography (12 g, 0-5% MeOH in DCM)
  8. customto afford a crude residue
  9. customThe crude residue was further purified by preparative HPLC (Waters, Acidic (0.1% Formic acid), Waters X-Select Prep-C18, 5 μm, 19×50 mm column, 30-60% MeCN in water)

Sources & evidence

ORD record
ord-cf956c47ac054f668ca2af14df5012f2
Source dataset
uspto-grants-2015_12
Patent number
US09221756B2

Reaction notes

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