1-Hydroxybenzotriazole → HCID 57920183, compound

HRID 19105Notes

Reaction equation

HRID 19105 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.[CH2:55]([C:57]1N=C(N)[S:59][N:58]=1)[CH3:56]>ClCCl>[CH2:55]([C:57]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]([CH3:14])[CH3:15])[S:59][N:58]=1)[CH3:56]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27564305-Amino-3-ethyl-1,2,4-thiadiazoleHCID 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]-amide

Product 1

HCID 57920183HCID 57920183, compoundYield 59.6%

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, 104 mg, 0.32 mmol) in dichloromethane (1.00 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (69 mg, 0.36 mmol) and 1-hydroxybenzotriazole (46 mg, 0.34 mmol). The resulting solution was stirred for 5 min before 3-ethyl-[1,2,4]thiadiazol-5-ylamine (50 mg, 0.39 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-ethyl-[1,2,4]thiadiazol-5-yl)-amide (83 mg, 59%) as a light yellow solid: HR-ES-MS m/z calculated for C20H23ClN4O3S [M+H]+ 435.1252, observed 435.1252; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.88 (d, J=6.4 Hz, 3H), 0.91 (d, J=6.4 Hz, 3H), 1.45 (br. s., 1H), 1.53-1.72 (m, 1H), 1.83 (br. s., 1H), 3.69 (s, 3H), 4.04 (s, 2H), 4.26 (d, J=18.4 Hz, 1H), 4.48 (d, J=18.4 Hz, 1H), 4.80 (s, 1H), 4.96 (dd, J=11.2, 4.5 Hz, 1H), 6.84 (d, J=8.5 Hz, 2H), 7.17 (d, J=8.5 Hz, 2H), 7.35 (td, J=7.8, 1.5 Hz, 1H), 7.45 (t, J=7.8 Hz, 1H), 7.51 (d, J=7.8 Hz, 1H), 7.64 (d, J=7.8 Hz, 1H), 13.28 (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-5c4c1e1024104f519adf919a143d84d3
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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