Carbamic chloride, N-methyl-N-phenyl- → HCID 59784104, compound

HRID 2079767Notes

Reaction equation

HRID 2079767 reaction equation
[CH3:1][N:2]([C@@H:10]([CH3:39])[C:11]([NH:13][C@H:14]([C:18]([N:20]1[CH2:25][CH2:24][NH:23][CH2:22][C@H:21]1[C:26]([NH:28][C@H:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH2:32][CH2:31][CH2:30]1)=[O:27])=[O:19])[CH:15]([CH3:17])[CH3:16])=[O:12])[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].CCN(C(C)C)C(C)C.[CH3:49][N:50]([C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)[C:51](Cl)=[O:52]>C(Cl)Cl>[C:5]([O:4][C:3](=[O:9])[N:2]([CH3:1])[C@@H:10]([CH3:39])[C:11]([NH:13][C@H:14]([C:18]([N:20]1[CH2:25][CH2:24][N:23]([C:51]([N:50]([CH3:49])[C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)=[O:52])[CH2:22][C@H:21]1[C:26]([NH:28][C@H:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH2:32][CH2:31][CH2:30]1)=[O:27])=[O:19])[CH:15]([CH3:17])[CH3:16])=[O:12])([CH3:7])([CH3:8])[CH3:6]

Participants

5

Reactant 3

HCID 77969Carbamic chloride, N-methyl-N-phenyl-2×HCID 81531Diisopropylethylamine2×HCID 59784098HCID 59784098, compound

Product 1

HCID 59784104HCID 59784104, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Intermediate 7 (175 mg, 0.322 mmol) is dissolved in anhydrous CH2Cl2 (15 mL), to which DIEA (70 μL, 0.40 mmol) is added. The solution is cooled to 0° C. and N-methyl-N-phenylcarbamoyl chloride (66 mg, 0.39 mmol) is added, the solution is subsequently warmed to room temperature for 4 h. N-Methyl-N-phenylcarbamoyl chloride (66 mg, 0.39 mmol) and DIEA (70 μL, 0.40 mmol) are added and the solution is stirred at room temperature for 15 h at room temperature. The solution is diluted with CH2Cl2 (50 mL) and washed with sat. NaHCO3 and brine. The solution is dried (MgSO4), filtered, and the solvent removed under reduced pressure to give the crude product as an oil. This material is purified by flash chromatography on silica gel (0-5% MeOH/CH2Cl2). The title compound is isolated as a white foam (168 mg, 77% yield): 1H NMR δ (CDCl3) 6.60-7.60 (m, 10H), 4.19-5.20 (m, 5H), 3.62 (“br d”, 1H, Jobs=13.2 Hz), 3.52 (“br d” 1H, Jobs=13.4 Hz), 2.56-3.28 (m, 10H), 1.72-2.10 (m, 5H), 1.47 and 1.45 (s, 9H total), 1.24-1.32 (br m, 3H), 0.88-1.12 (m, 2H), 1.09 (br d, 1H, J=6.7 Hz), 0.90 (dd, 2H, J=7.0, 2.6 Hz), 0.78 (br d, 2H, J=6.7 Hz), 0.66 (br d, 2H, 6.7 Hz; LCMS (APCl+) 678.6 (MH+, 100%).

Workup

  1. additionis added
  2. temperaturethe solution is subsequently warmed to room temperature for 4 h
  3. washwashed with sat. NaHCO3 and brine
  4. dry with materialThe solution is dried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. customto give the crude product as an oil
  8. customThis material is purified by flash chromatography on silica gel (0-5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-3be41b49b2374ab8b10b9d819d6f24da
Source dataset
uspto-grants-2011_04
Patent number
US07932255B2

Reaction notes

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