Nitrogen → HCID 86636032, compound

HRID 449033Notes

Reaction equation

HRID 449033 reaction equation
N#N.C(OC(N1CC([CH:14]([C:28]2[C:33]([Cl:34])=[N:32][CH:31]=[CH:30][N:29]=2)[C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:17][CH:16]=2)C1C(=O)N)=O)(C)(C)C.[CH3:38][C:39]#[N:40].[CH3:41][N:42]([CH:44]=[O:45])[CH3:43].O=P(Cl)(Cl)Cl.[OH2:51]>>[C:15]([O:45][C:44]([N:42]1[CH2:43][CH:38]([C:39]2[N:29]3[CH:30]=[CH:31][N:32]=[C:33]([Cl:34])[C:28]3=[C:14]([C:15]3[CH:20]=[CH:19][C:18]([O:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[CH:17][CH:16]=3)[N:40]=2)[CH2:41]1)=[O:51])([CH3:20])([CH3:16])[CH3:14]

Participants

7

Reactant 6

HCID 947NitrogenHCID 962WaterHCID 6228DimethylformamideHCID 6342AcetonitrileHCID 24813Phosphorus oxychlorideHCID 87202939HCID 87202939, compound

Product 1

HCID 86636032HCID 86636032, compound

Procedure

In an oven-dried flask filled with N2 was added 3-[(3-chloropyrazin-2-yl)-(4-phenoxyphenyl)-methyl]-carbamoylazetidine-1-carboxylic acid tert-butyl ester (110 mg, 0.00022 mol), MeCN (3 mL, 0.07 mol) and DMF (0.3 mL, 0.004 mol). POCl3 was added dropwise at 0° C. The reaction was warmed up to rt and stirred at that temp overnight. The excess of POCl3 was removed under reduced pressure and the residue was quenched with 2 N NH3 in i-PrOH at 0° C. with vigorous stirring to adjust pH to 9. The crude reaction mixture was then charged with water and the aqueous layer was washed with DCM. The combined organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. Purification by prep TLC using 3% NH3 in MeOH in DCM afforded 45 mg of the title compound as a yellow oil. The compound was carried on to the next step. MS (ES+): m/z 477.02 (100)[MH+]. HPLC: tR=4.17 min (Open Lynx, polar—5 min).

Workup

  1. customThe excess of POCl3 was removed under reduced pressure
  2. customthe residue was quenched with 2 N NH3 in i-PrOH at 0° C.
  3. stirringwith vigorous stirring
  4. customThe crude reaction mixture
  5. washthe aqueous layer was washed with DCM
  6. dry with materialThe combined organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification by prep TLC

Sources & evidence

ORD record
ord-1039395060e6440db9a384381b9305b8
Source dataset
uspto-grants-2013_07
Patent number
US08481733B2

Reaction notes

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