Phosgene → HCID 58997104, compound

HRID 251175Notes

Reaction equation

HRID 251175 reaction equation
[CH3:1][C:2]1[C:3]([CH2:8][N:9]([CH2:16][C:17]2[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[N:4][CH:5]=[CH:6][CH:7]=1.CCN(CC)CC.[C:31](Cl)(Cl)=[O:32].CCN(C(C)C)C(C)C.Cl.[CH3:45][NH:46][OH:47]>C1(C)C=CC=CC=1.C(Cl)Cl>[OH:47][N:46]([CH3:45])[C:31]([N:13]1[CH2:14][CH2:15][CH:10]([N:9]([CH2:16][C:17]2[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:8][C:3]2[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][N:4]=2)[CH2:11][CH2:12]1)=[O:32]

Participants

8

Reactant 5

HCID 6371PhosgeneHCID 8471TriethylamineHCID 77906N-methylhydroxylamine hydrochlorideHCID 81531DiisopropylethylamineHCID 58996965Bis-(3-methyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

Product 1

HCID 58997104HCID 58997104, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of COMPOUND 249 (236 mg, 0.760 mmol) in toluene (20 mL) and Et3N (0.45 mL, 3.42 mmol) was added phosgene solution in toluene (20 wt %, 0.519 mL, 1.14 mmol). The mixture was stirred at 0° C. for 2 hours, was then warmed up to room temperature and solvent was removed under reduced pressure (high vac.) to yield a yellow solid. Half of the solid (0.380 mmol) was dissolved in CH2Cl2 (10 mL) and DIPEA (0.5 mL) was added followed by N-methylhydroxylamine hydrochloride (48 mg, 0.57 mmol). The mixture was stirred at room temperature for 17 hours. Solvent was removed under reduced pressure and the residue was dissolved in CH2Cl2 (20 mL), extracted with saturated NaHCO3 (20 mL), dried over MgSO4, filtered and concentrated. The crude material was purified by column chromatography on silica gel (9:1:0.1 CH2Cl2:MeOH:NH4OH) to provide COMPOUND 325 as white solid (81 mg, 55%). 1H NMR (CDCl3) δ 1.60-1.73 (m, 3H), 1.92-2.00 (m, 2H), 2.09 (s, 6H), 2.65-2.76 (m, 3H), 2.95 (s, 3H), 3.83 (s, 4H), 4.12-4.18 (m, 2H), 7.09 (dd, 2H, J=4.2, 7.5 Hz), 7.37 (d, 2H, J=7.5 Hz), 8.34 (d, 2H, J=4.2 Hz); 13C NMR (CDCl3) δ 18.0, 27.1, 44.3, 45.5, 54.6, 57.4, 122.5, 133.4, 138.2, 145.9, 157.0, 165.8; ES-MS m/z 384 (M+H). Anal. Calcd. for C21H29N5O2.0.2H2O.0.5 CH2Cl2: C, 60.12; H, 7.13; N, 16.30. Found: C, 60.06; H, 7.09; N, 16.32.

Workup

  1. temperaturewas then warmed up to room temperature
  2. customsolvent was removed under reduced pressure (high vac.)
  3. customto yield a yellow solid
  4. stirringThe mixture was stirred at room temperature for 17 hours
  5. customSolvent was removed under reduced pressure
  6. dissolutionthe residue was dissolved in CH2Cl2 (20 mL)
  7. extractionextracted with saturated NaHCO3 (20 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude material was purified by column chromatography on silica gel (9:1:0.1 CH2Cl2:MeOH:NH4OH)

Sources & evidence

ORD record
ord-1ce051f3b45849f087f4e1068454375b
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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