Triethylamine → HCID 117832240, compound

HRID 2280122Notes

Reaction equation

HRID 2280122 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][NH:19][CH2:18]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.[CH:30]1([CH2:33][C:34](O)=O)[CH2:32][CH2:31]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>O.C(#N)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][N:19]([CH2:34][CH2:33][CH:30]4[CH2:32][CH2:31]4)[CH2:18]3)=[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 8471Triethylamine2×HCID 757711-HydroxybenzotriazoleHCID 138440Cyclopropaneacetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86714273HCID 86714273, compound

Product 1

HCID 117832240HCID 117832240, compoundYield 54.2%

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent2×

Procedure

To a solution of (S)-4-amino-5(piperidine-3-ylmethoxy)-1H-benzo[c][1,2,6]thiadiazin 2,2-dioxide hydrochloride (Example 2a, 694 mg, 2.0 mmol) in H2O/ACN (5 mL, 1:1) was added triethylamine (228 uL, 2.0 mmol). After stirring at room temperature for 5 min a solution of 2-cyclopropylacetic acid (200 mg, 2.0 mmol), HOBt (272 mg. 2.0 mmol), and EDCI-HCl (382 mg. 2.0 mmol) in H2O/ACN (5 mL, 1:1) was added to the mixture. An additional equivalent of triethylamine (228 uL, 2.0 mmol) was added and the reaction mixture was stirred at room temperature overnight. The product crashed out of solution and is collected by vacuum filtration. The compound was purified via preparative RP HPLC (10 to 90% EtOH in water) then diluted with 10 mL water and 200 mg of NaHCO3 was added. The solution was heated at 90° C. for 20 minutes until all the compound was dissolved then cooled to 0° C. and neutralized with 1N HCl solution. The product precipitated out and was collected by filtration and dried to provide the title compound (410 mg, 52.3%). 1H NMR (DMSO-d6, 400 MHz, 80° C.): 0.12 (br s, 2H), 0.44 (m, 2H), 0.96 (br s, 1H), 1.42 (m, 2H), 1.70 (m, 1H), 1.88 (m, 1H), 1.98 (br s, 1H), 2.09 (m, 1H), 2.26 (br s, 2H), 2.91 (m, 2H), 3.67 (br s, 0.5H), 3.85 (br s, 0.5H), 4.09 (m, 3H), 6.65 (d, J=8.4 Hz, 1H), 6.71 (d, J=8.4 Hz, 1H), 7.46 (t, J=8.4 Hz, 1H), 7.75 (br s, 1H), 8.16 (br s, 1H), 10.79 (s, 1H). M+H=393.

Workup

  1. additionwas added to the mixture
  2. filtrationis collected by vacuum filtration
  3. customThe compound was purified via preparative RP HPLC (10 to 90% EtOH in water)
  4. additionthen diluted with 10 mL water and 200 mg of NaHCO3
  5. additionwas added
  6. temperatureThe solution was heated at 90° C. for 20 minutes until all the compound
  7. dissolutionwas dissolved
  8. temperaturethen cooled to 0° C. and neutralized with 1N HCl solution
  9. customThe product precipitated out
  10. filtrationwas collected by filtration
  11. customdried

Sources & evidence

ORD record
ord-50e9fbd1f5ea45dcb6b9eda9de6344f6
Source dataset
uspto-grants-2015_09
Patent number
US09138013B2

Reaction notes

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