Phosgene → HCID 58997079, compound

HRID 251174Notes

Reaction equation

HRID 251174 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].[NH2:35][OH:36].Cl>C1(C)C=CC=CC=1.C(Cl)Cl>[OH:36][NH:35][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

7

Reactant 4

HCID 6371PhosgeneHCID 8471Triethylamine2×HCID 443297Hydroxyamine hydrochlorideHCID 58996965Bis-(3-methyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

Product 1

HCID 58997079HCID 58997079, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of COMPOUND 249 (144 mg, 0.465 mmol) in toluene (20 mL) and Et3N (0.40 mL, 3.34 mmol) was added phosgene solution in toluene (20 wt %, 0.317 mL, 0.697 mmol). The mixture was stirred at 0° C. for 3 hours, was then warmed up to room temperature and solvent was removed under reduced pressure (high vac.) to yield a yellow solid. The solid was dissolved in CH2Cl2 (15 mL) and Et3N (0.194 mL, 1.40 mmol) was added followed by NH2OH.HCl (48 mg, 0.700 mmol). The mixture was stirred at room temperature for 17 hours. Solvent was removed under reduced pressure and the residue was purified by radial chromatography on silica gel (9:1:0.2 CH2Cl2:MeOH:NH4OH) to provide COMPOUND 324 as white solid (112 mg, 60%). 1H NMR (CDCl3) δ 1.61-1.73 (m, 3H), 1.92-2.00 (m, 2H), 2.08 (s, 6H), 2.65-2.72 (m, 3H), 3.81 (s, 4H), 4.01-4.06 (m, 2H), 6.72 (br s, 1H), 7.09 (dd, 2H, J=4.8, 7.8 Hz), 7.37 (d, 2H, J=7.8 Hz), 8.34 (d, 2H, J=4.8 Hz); 13C NMR (CDCl3) δ 18.0, 26.9, 43.8, 54.6, 57.3, 122.5, 133.4, 138.1, 145.9, 157.0, 160.7; ES-MS m/z 370 (M+H). Anal. Calcd. for C20H27N5O2.0.4 CH2Cl2: C, 60.73; H, 6.95; N, 17.36. Found: C, 61.07; H, 7.19; N, 17.09.

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. customthe residue was purified by radial chromatography on silica gel (9:1:0.2 CH2Cl2:MeOH:NH4OH)

Sources & evidence

ORD record
ord-2d6678faa29d46758e6f2c77eae77fd1
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

Loading…