Dimethylformamide → HCID 57681091, compound

HRID 1163137Notes

Reaction equation

HRID 1163137 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([CH2:17][C:18](=O)[NH:19][CH:20]([C:37]2[C:42]([Cl:43])=[N:41][CH:40]=[CH:39][N:38]=2)[C:21]2[CH:30]=[C:29]3[C:24]([CH:25]=[CH:26][C:27]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)=[N:28]3)=[CH:23][CH:22]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=P(Cl)(Cl)Cl.CN(C=O)C>C(#N)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][CH:14]([CH2:17][C:18]2[N:38]3[CH:39]=[CH:40][N:41]=[C:42]([Cl:43])[C:37]3=[C:20]([C:21]3[CH:30]=[C:29]4[C:24]([CH:25]=[CH:26][C:27]([C:31]5[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=5)=[N:28]4)=[CH:23][CH:22]=3)[N:19]=2)[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 53629034HCID 53629034, compound

Product 1

HCID 57681091HCID 57681091, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
55 °C

Procedure

A solution of 4-({[(3-chloro-pyrazin-2-yl)-(2-phenyl-quinolin-7-yl)-methyl]-carbamoyl}-methyl)-piperidine-1-carboxylic acid benzyl ester in anhydrous acetonitrile (165 mL) was charged with POCl3 (2.03 mL, 21.84 mmol) and DMF (2.15 mL) and heated to 55° C. under N2 condition. After 2 h, LC/MS and TLC analysis showed the reaction to be completed. The reaction mixture was concentrated in vacuo, diluted with CH2Cl2, and quenched with 2N (7N NH3) in 2-propanol to pH 9. 2-Propanol was removed in vacuo. The crude product was purified by silica gel flash chromatography (loaded with 40% EtOAc/Hexanes, and run 50% EtOAc/Hexanes→80% EtOAc/Hexanes), which afforded the desired product; 1H NMR (400 MHz, DMSO-d) 5 ppm 8.53 (1H, d, J=8.52), 8.45 (1H, d, J=5.00), 8.31 (3H, m), 8.21 (1H, d, J=8.66), 8.08 (1H, d, J=8.47), 7.56 (3H, m), 7.49 (1H, d, J=5.00), 7.34 (5H, m), 5.07 (2H, s), 4.02 (2H, d, J=12.8), 3.32 (2H, s), 3.11 (2H, d, J=6.92), 2.82 (1H, m), 2.13 (1H, m), 1.73 (2H, d, J=12.26), 1.21 (2H, m); MS (ES+): m/z 589.97 (5) [MH+]; HPLC: tR=3.72 min (OpenLynx, polar—5 min).

Workup

  1. customthe reaction
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. additiondiluted with CH2Cl2
  4. customquenched with 2N (7N NH3) in 2-propanol to pH 9
  5. custom2-Propanol was removed in vacuo
  6. customThe crude product was purified by silica gel flash chromatography (loaded with 40% EtOAc/Hexanes, and run 50% EtOAc/Hexanes→80% EtOAc/Hexanes), which

Sources & evidence

ORD record
ord-32644e393abf40aab63570cd05fbbd9b
Source dataset
uspto-grants-2010_10
Patent number
US07820662B2

Reaction notes

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