1-Hydroxybenzotriazole → HCID 57920043, compound

HRID 19101Notes

Reaction equation

HRID 19101 reaction equation
OC(C)(C)CN1C=CC(NC(=O)[C@@H](N2CC(O[C:22]3[CH:27]=[CH:26][CH:25]=C[C:23]=3[Cl:28])=CC2=O)CC(C)C)=N1.Cl.[CH3:34][N:35](C)[CH2:36]CCN=C=NCC.O[N:46]1C2C=CC=CC=2N=N1.[CH:55]1([CH2:60][C@H:61]([N:71]2[CH2:75][C:74]([O:76][CH3:77])=[CH:73][C:72]2=[O:78])[C:62]([NH:64][C:65]2[S:66]C(F)=[CH:68][N:69]=2)=[O:63])[CH2:59]CC[CH2:56]1>ClCCl>[CH3:34][N:35]([CH3:36])[C:68]1[N:69]=[C:65]([NH:64][C:62](=[O:63])[C@@H:61]([N:71]2[CH2:75][C:74]([O:76][C:77]3[CH:25]=[CH:26][CH:27]=[CH:22][C:23]=3[Cl:28])=[CH:73][C:72]2=[O:78])[CH2:60][CH:55]([CH3:56])[CH3:59])[S:66][N:46]=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 44253055HCID 44253055, compound

Product 1

HCID 57920043HCID 57920043, compoundYield 36%

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, 93 mg, 0.29 mmol) in dichloromethane (1.00 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (60 mg, 0.31 mmol) and 1-hydroxybenzotriazole (40 mg, 0.30 mmol). The resulting solution was stirred for 5 min before N3,N3-dimethyl-[1,2,4]thiadiazole-3,5-diamine (prepared in German Patent DE959191 Example 8, 50 mg, 0.35 mmol) was added and the resulting mixture stirred at 25° C. overnight. The mixture was washed with saturated aqueous ammonium chloride solution (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-dimethylamino-[1,2,4]thiadiazol-5-yl)-amide (47 mg, 36%) as a yellow solid: HR-ES-MS m/z calculated for C20H24ClN5O3S [M+H]+ 450.1361, observed 450.1360; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.89 (d, J=6.4 Hz, 3H), 0.93 (d, J=6.4 Hz, 3H), 1.44 (br. s., 1H), 1.51-1.72 (m, 1H), 1.72-1.98 (m, 1H), 3.02 (s, 6H), 4.25 (d, J=18.4 Hz, 1H), 4.50 (d, J=18.4 Hz, 1H), 4.81 (s, 1H), 4.97 (dd, J=10.9, 4.5 Hz, 1H), 7.36 (td, J=7.8, 1.5 Hz, 1H), 7.45 (td, J=7.8, 1.4 Hz, 1H), 7.52 (dd, J=7.8, 1.5 Hz, 1H), 7.64 (dd, J=7.8, 1.4 Hz, 1H), 13.08 (s, 1H).

Workup

  1. additionwas added
  2. washThe mixture was washed with saturated aqueous ammonium chloride solution (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-d1e9fb0213874a18a1adb61a1ef5447b
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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