Dimethylcarbamoyl Chloride → HCID 67418508, compound

HRID 1727442Notes

Reaction equation

HRID 1727442 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([C@@H:12]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH2:28][CH3:29])[CH:20]=1)[CH2:13][C:14]([N:16]([CH3:18])[CH3:17])=[O:15])[CH2:7]2.[CH3:30][N:31]([CH3:35])[C:32](Cl)=[O:33]>C1COCC1>[CH3:30][N:31]([CH3:35])[C:32](=[O:33])[NH:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([C@@H:12]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH2:28][CH3:29])[CH:20]=1)[CH2:13][C:14]([N:16]([CH3:18])[CH3:17])=[O:15])[CH2:7]2

Participants

4

Reactant 2

HCID 6598Dimethylcarbamoyl ChlorideHCID 66718493HCID 66718493, compound

Product 1

HCID 67418508HCID 67418508, compoundYield 34.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (3R)-3-(7-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(3-ethoxy-4-methoxy-phenyl)-N,N-dimethyl-propionamide (1.1 g, 2.8 mmol) and dimethylcarbamyl chloride (0.5 mL, 5.4 mmol) in THF (5 mL) was heated to reflux for 2 days. The solvent was removed in vacuo to give a solid, which was purified with prep HPLC to give (3R)-3-[7-(3,3-dimethyl-ureido)-1-oxo-1,3-dihydro-isoindol-2-yl]-3-(3-ethoxy-4-methoxy-phenyl)-N,N-dimethyl-propionamide as a white solid (450 mg, 34% yield): mp 105-107° C.; 1HNMR (CDCl3) δ 1.44 (t, J=7 Hz, 3H, CH3), 2.90 (s, 3H, CH3), 3.05 (dd, J=6, 16Hz, 1H, CHH), 3.09 (s, 9H,3 CH3), 3.46 (dd, J=9.15 Hz, 1H, CHH), 3.85 (s, 3H, CH3), 4.07 (q, J=7 Hz, 2H, CH2), 4.22 (d, J=17 Hz, 1H, NCHH), 4.41 (d, J=17 Hz, 1H, NCHH), 5.63 (dd, J=6, 9Hz, 1H, NCH), 6.91-6.96 (m, 4H, Ar), 7.39 (t, J=8 Hz, 1H, Ar), 8.30 (d, J=8 Hz, 1H, Ar), 9.99 (s, 1H, NH); 13 CNMR (CDCl3) δ 14.76, 35.57, 36.31, 36.38, 37.45, 48.70, 53.35, 55.97, 64.53, 111.46, 112.63, 115.07, 116.27, 117.57, 119.16, 131.90, 133.02, 139.61, 141.54, 148.55, 149.08, 155.49, 149.69, 170.15. Analy. Calculated for C25H32N4O5+1.2 H2O: C 61.26; H 7.07; N 11.43; H2O 4.41. Found: C 60.89; H 6.95; N 11.10; H2O 4.04.

Workup

  1. temperatureto reflux for 2 days
  2. customThe solvent was removed in vacuo
  3. customto give a solid, which
  4. customwas purified with prep HPLC

Sources & evidence

ORD record
ord-301206547c7f4dd4bc96d5776eb1b145
Source dataset
uspto-grants-2009_02
Patent number
US07495112B2

Reaction notes

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