Triethylamine → HCID 10413688, compound

HRID 1787959Notes

Reaction equation

HRID 1787959 reaction equation
[NH2:1][CH2:2][CH2:3][C@@H:4]([N:16]1[C:24](=[O:25])[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][C:22]=2[NH:26][C:27]([CH:29]2[CH2:31][CH2:30]2)=[O:28])[CH2:17]1)[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]([O:13][CH2:14][CH3:15])[CH:6]=1.C(N(CC)CC)C.[CH3:39][S:40](Cl)(=[O:42])=[O:41]>C(Cl)Cl>[CH2:14]([O:13][C:7]1[CH:6]=[C:5]([C@H:4]([N:16]2[C:24](=[O:25])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][C:22]=3[NH:26][C:27]([CH:29]3[CH2:31][CH2:30]3)=[O:28])[CH2:17]2)[CH2:3][CH2:2][NH:1][S:40]([CH3:39])(=[O:42])=[O:41])[CH:10]=[CH:9][C:8]=1[O:11][CH3:12])[CH3:15]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 10342247HCID 10342247, compound

Product 1

HCID 10413688HCID 10413688, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (1R)-cyclopropanecarboxylic acid {2-[3-amino-1-(3-ethoxy-4-methoxy-phenyl)-propyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide (0.45 g, 1.1 mmol) and triethylamine (0.3 mL, 2 mmol) in methylene chloride (10 mL) was added methane sulfonyl chloride (0.10 mL, 1.3 mmol) at 0° C. After 3 hrs, the mixture was extracted with methylene chloride (20 mL) and water (20 mL). The organic layer was washed with HCl (1N, 20 mL), sodium hydrogen carbonate (sat 20 mL), brine (20 mL), and dried over MgSO4. The solvent was removed in vacuo to give a solid, which was purified with chromatography (Silca Gel) to give (1R)-cyclopropanecarboxylic acid {2-[1-(3-ethoxy-4-methoxy-phenyl)-3-methanesulfonylamino-propyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide as a white solid (320 mg, 58% yield): mp, 93-95° C.; 1H NMR (CDCl3) δ 0.89-0.93 (m, 2H, CH2), 1.08-1.10 (m, 2H, CH2), 1.42 (t, J=7 Hz, 3H, CH3), 1.65-1.72 (m, 1H, CH), 2.27-2.32 (m, 2H, CH2), 2.94 (s, 3H, CH3), 2.97-3.06 (m, 1H, CHH), 3.85 (s, 3H, CH3), 3.50 (d, J=17 Hz, 1H, NCHH), 4.04 (q, J=7 Hz, 2H, CH2), 4.18 (d, J=17 Hz, 1H, NCHH), 5.51 (dd, J=6, 9 Hz, 1H, NCH), 5.60-5.62 (m, 1H, NH), 6.8-6.99 (m, 4H, Ar), 7.42 (t, J=8 Hz, 1H, Ar), 8.42 (d, J=8 Hz, 1H, Ar), 10.47 (s, 1H, NH); 13C NMR (CDCl3) δ 8.35, 14.76, 16.19, 32.26, 40.24, 40.65, 46.05, 51.12, 55.98, 64.63, 111.50, 112.83, 116.86, 116.94, 117.84, 119.64, 130.31, 133.43, 138.02, 141.44, 148.72, 149.41, 170.07, 172.72; Anal Calcd for C25H31N3O6S+0.35H2O: C, 59.12; H, 6.29; N, 8.27, H2O 1.26. Found: C, 59.42; H, 6.16; N, 8.05, H2O 1.24.

Workup

  1. extractionthe mixture was extracted with methylene chloride (20 mL) and water (20 mL)
  2. washThe organic layer was washed with HCl (1N, 20 mL), sodium hydrogen carbonate (sat 20 mL), brine (20 mL)
  3. dry with materialdried over MgSO4
  4. customThe solvent was removed in vacuo
  5. customto give a solid, which
  6. customwas purified with chromatography (Silca Gel)

Sources & evidence

ORD record
ord-818c2b18a9904f71addd77ccaff06faa
Source dataset
uspto-grants-2009_03
Patent number
US07511072B2

Reaction notes

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