1-Hydroxybenzotriazole → HCID 44252462, compound

HRID 19109Notes

Reaction equation

HRID 19109 reaction equation
OC(C)(C)CN1C=C[C:6]([NH:9][C:10](=[O:30])[C@@H:11]([N:16]2[CH2:20][C:19]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[Cl:28])=[CH:18][C:17]2=[O:29])[CH2:12][CH:13]([CH3:15])[CH3:14])=[N:5]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.NC1[S:60][N:59]=[C:58]([CH2:61][C:62](=[O:64])[CH3:63])N=1>ClCCl>[O:64]=[C:62]([CH3:63])[CH2:61][C:58]1[N:5]=[C:6]([NH:9][C:10](=[O:30])[C@@H:11]([N:16]2[CH2:20][C:19]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[Cl:28])=[CH:18][C:17]2=[O:29])[CH2:12][CH:13]([CH3:15])[CH3:14])[S:60][N:59]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 44240794(S)-2-[4-(2-Chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amideHCID 547753311-(5-Amino-1,2,4-thiadiazol-3-yl)propan-2-one

Product 1

HCID 44252462HCID 44252462, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (prepared as in Example 64, 90 mg, 0.28 mmol) in dichloromethane (1.00 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (67 mg, 0.35 mmol) and 1-hydroxybenzotriazole (41 mg, 0.30 mmol). The resulting solution was stirred for 5 min before 1-(5-amino-1,2,4-thiadiazol-3-yl)-2-propanone (56 mg, 0.29 mmol) was added and the resulting mixture stirred at 25° C. overnight. The mixture was washed with saturated ammonium chloride (1 mL), evaporated and the crude product purified by HPLC (Gilson semi-prep; Supelcosil ABZ+Plus 12 μM 25 cm×21.2 mm column 20-95% acetonitrile/water gradient) which afforded (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [3-(2-oxo-propyl)-[1,2,4]thiadiazol-5-yl]-amide (51 mg, 40%) as a light yellow solid: HR-ES-MS m/z calculated for C21H23ClN4O4S [M+H]+ 463.1202, observed 463.1202; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.91 (d, J=6.6 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H), 1.47 (br. s., 1H), 1.59-1.76 (m, 1H), 1.79-1.95 (m, 1H), 2.18 (s, 3H), 4.00 (s, 2H), 4.29 (d, J=18.4 Hz, 1H), 1.59 (d, J=18.4 Hz, 1H), 4.83 (s, 1H), 5.01 (dd, J=10.9, 4.8 Hz, 1H), 7.37 (td, J=7.5, 1 Hz, 1H), 7.47 (t, J=7.5 Hz, 1H), 7.54 (m, J=7.5 Hz, 1H), 7.66 (d, J=7.5 Hz, 1H), 13.37 (s, 1H).

Workup

  1. additionwas added
  2. washThe mixture was washed with saturated ammonium chloride (1 mL)
  3. customevaporated
  4. customthe crude product purified by HPLC (Gilson semi-prep; Supelcosil ABZ+Plus 12 μM 25 cm×21.2 mm column 20-95% acetonitrile/water gradient) which

Sources & evidence

ORD record
ord-e65c25dea95f42589c0239c621e7e795
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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