Dimethylformamide → HCID 178501055, compound

HRID 448963Notes

Reaction equation

HRID 448963 reaction equation
[Cl:1][C:2]1[C:3]([CH2:8][NH:9][C:10]([C@H:12]2[CH2:17][CH2:16][C@H:15]([C:18]([O:20][CH3:21])=[O:19])[CH2:14][CH2:13]2)=O)=[N:4][CH:5]=[CH:6][N:7]=1.CN(C=O)C.O=P(Cl)(Cl)Cl>CC#N>[Cl:1][C:2]1[C:3]2[N:4]([C:10]([C@H:12]3[CH2:17][CH2:16][C@H:15]([C:18]([O:20][CH3:21])=[O:19])[CH2:14][CH2:13]3)=[N:9][CH:8]=2)[CH:5]=[CH:6][N:7]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 178501155HCID 178501155, compound

Product 1

HCID 178501055HCID 178501055, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

trans-Methyl 4-({[(3-chloropyrazin-2-yl)methyl]amino}carbonyl)-cyclohexane carboxylate (29.00 g, 93.02 mmol) was dissolved in anhydrous MeCN (930 mL), anhydrous DMF (9 mL) and POCl3 (10.4 mL, 110 mmol) and heated at 55° C. under nitrogen for 3 h. The reaction mixture was concentrated in vacuo, then, the solid residue was taken up in DCM, then, basified to pH 10 with 2M ammonia in isopropanol. The mixture was concentrated in vacuo, re-dissolved in DCM, and then loaded onto TEA-basified silica gel. The crude product was purified by a silica gel column chromatography (eluted with 2:3 EtOAc/DCM) to obtain the title compound as a yellow powder; 1H NMR (CDCl3, 400 MHz) δ 1.63 (ddd, J=13.2, 13.2, 13.2, 3.2 Hz, 2H), 1.85 (ddd, J=13.2, 13.2, 13.2, 2.8 Hz, 2H), 2.10 (dd, J=14.4, 3.2 Hz, 2H), 2.19 (dd, J=14.0, 3.2 Hz, 2H), 2.46 (tt, J=12.4, 3.6 Hz, 1H), 2.96 (tt, J=11.6, 3.2 Hz, 1H), 3.70 (s, 3H), 7.33 (dd, J=5.2, 1.2 Hz, 1H), 7.61 (d, J=4.8 Hz, 1H), 7.79 (s, 1H). MS (ES+): m/z 294.17/296.14 (100/86) [MH+]. HPLC: tR=2.85 min (OpenLynx, polar—5 min).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. concentrationThe mixture was concentrated in vacuo
  3. dissolutionre-dissolved in DCM
  4. customThe crude product was purified by a silica gel column chromatography (eluted with 2:3 EtOAc/DCM)

Sources & evidence

ORD record
ord-b5ee0d79d43d44ac80ba20a6e13a3997
Source dataset
uspto-grants-2013_07
Patent number
US08481733B2

Reaction notes

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