Triethylamine → HCID 73213733, compound

HRID 332959Notes

Reaction equation

HRID 332959 reaction equation
Cl.[NH2:2][C:3]1[C:4]2[C:14]([O:15][CH2:16][C@H:17]3[CH2:22][CH2:21][CH2:20][CH2:19][NH:18]3)=[CH:13][CH:12]=[CH:11][C:5]=2[NH:6][S:7](=[O:10])(=[O:9])[N:8]=1.C(N(CC)CC)C.[CH3:30][CH:31]([CH3:36])[CH2:32][C:33](O)=[O:34].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[NH2:2][C:3]1[C:4]2[C:14]([O:15][CH2:16][C@H:17]3[CH2:22][CH2:21][CH2:20][CH2:19][N:18]3[C:33](=[O:34])[CH2:32][CH:31]([CH3:36])[CH3:30])=[CH:13][CH:12]=[CH:11][C:5]=2[NH:6][S:7](=[O:9])(=[O:10])[N:8]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 10430Isovaleric AcidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86714281HCID 86714281, compound

Product 1

HCID 73213733HCID 73213733, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (R)-4-amino-5-(piperidin-2-ylmethoxy)-1H-benzo[c][1,2,6]thiadiazine 2,2-dioxide hyrochloride (Example 15a, 500 mg, 1.44 mmol) in DMF (12 mL) was added triethylamine (399 uL, 2.88 mmol), 3-methylbutanoic acid (159 uL, 1.44 mmol), EDCI-HCl (276 mg, 1.44 mmol), and HOBt (220 mg, 1.44 mmol). The reaction mixture was stirred at room temperature, under nitrogen for 18 hrs, then was filtered and purified by HPLC (10-90% acetonitrile in water). The pure fractions were combined, concentrated and crystallized from ethanol and water to give the title compound as a white solid (73 mg, 13% yield). 1H NMR (400 MHz, DMSO-d6, 80° C.) δ0.89 (d, J=6.8 Hz, 6H), 1.37 (m, 1H), 1.51-1.70 (m, 4H), 1.78 (d, J=12.8 Hz, 1H), 2.01 (m, 1H), 2.13-2.27 (m, 2H), 3.02 (br s, 1H), 3.89 (br s, 1H), 4.18 (br s, 1H), 4.48 (t, J=9.2 Hz, 1H), 5.02 (br s, 1H), 6.63 (d, J=8.0 Hz, 1H), 6.83 (d, J=8.8 Hz, 1H), 7.42 (t, J=8.4 Hz, 1H), 7.82 (br s, 2H), 10.63 (s, 1H). MS 395 (MH+).

Workup

  1. filtrationwas filtered
  2. custompurified by HPLC (10-90% acetonitrile in water)
  3. concentrationconcentrated
  4. customcrystallized from ethanol and water

Sources & evidence

ORD record
ord-d7baccd444f946f288de5513c1f0d975
Source dataset
uspto-grants-2014_11
Patent number
US08877922B2

Reaction notes

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