Phosgene → HCID 58997205, compound

HRID 251179Notes

Reaction equation

HRID 251179 reaction equation
[NH:1]1[CH2:4][CH:3]([CH2:5][N:6]([CH2:15][C:16]2[C:21]([CH3:22])=[CH:20][CH:19]=[CH:18][N:17]=2)[CH2:7][C:8]2[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][N:9]=2)[CH2:2]1.CCN(C(C)C)C(C)C.[C:32](Cl)(Cl)=[O:33].[NH2:36][OH:37].Cl.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1>[OH:37][NH:36][C:32]([N:1]1[CH2:4][CH:3]([CH2:5][N:6]([CH2:7][C:8]2[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][N:9]=2)[CH2:15][C:16]2[C:21]([CH3:22])=[CH:20][CH:19]=[CH:18][N:17]=2)[CH2:2]1)=[O:33]

Participants

7

Reactant 5

HCID 6371PhosgeneHCID 81531Diisopropylethylamine2×HCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 67271892HCID 67271892, compound

Product 1

HCID 58997205HCID 58997205, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a 0° C. solution of azetidin-3-ylmethyl-bis(3-methyl-pyridin-2-ylmethyl)-amine from above (134 mg, 0.452 mmol) in toluene (5 mL) and DIPEA (0.20 mL, 0.90 mmol) was added phosgene solution in toluene (20 wt %, 0.247 mL, 0.543 mmol). The reaction mixture was warmed to room temperature and was stirred for 1.5 hours. The volatiles were removed under reduced pressure and the remaining yellow solid was dissolved in DMF (5 mL). DIPEA (1 mL) and NH2OH.HCl (180 mg, 2.56 mmol) were added and the mixture was stirred for 17 hours at room temperature. Saturated NaHCO3 (15 mL) was added and the mixture was extracted with CH2Cl2 (3×30 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated. The crude material was purified by radial chromatography (10:1:0.2 CH2Cl2:MeOH:NH4OH) on silica gel to provide COMPOUND 330 (61 mg, 38%) as a white solid. 1H NMR (MeOH-d4) δ 2.14 (s, 6H), 2.69-2.72 (m, 2H), 2.82-2.85 (m, 1H), 3.25-3.31 (m, 2H), 3.73 (s, 4H), 3.93 (dd, 2H, J=8.4, 8.4 Hz), 7.26 (dd, 2H, J=4.5, 7.5 Hz), 7.59 (d, 2H, J=7.5 Hz), 8.29 (d, 2H, J=4.5 Hz); 13C NMR (DMSO-d6) δ 18.5, 29.3, 55.3, 60.3, 60.6, 124.9, 136.0, 140.8, 146.9, 157.8, 164.2; ES-MS m/z 378 (M+Na). Anal. Calcd. for C19H25N5O2.0.6H2O.0.9 CH2Cl2: C, 53.99; H, 6.37; N, 15.82. Found: C, 54.27; H, 6.33; N, 16.10.

Workup

  1. customThe volatiles were removed under reduced pressure
  2. dissolutionthe remaining yellow solid was dissolved in DMF (5 mL)
  3. stirringthe mixture was stirred for 17 hours at room temperature
  4. extractionthe mixture was extracted with CH2Cl2 (3×30 mL)
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified by radial chromatography (10:1:0.2 CH2Cl2:MeOH:NH4OH) on silica gel

Sources & evidence

ORD record
ord-71172ffad1b74ce5a215261a1fd9a70e
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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