1-Hydroxybenzotriazole → (5-{(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoylamino}-[1,2,4]thiadiazol-3-yl)-acetic acid allyl ester

HRID 19106Notes

Reaction equation

HRID 19106 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)[CH2:36][CH2:37][CH2:38]N=C=NCC.ON1C2C=CC=CC=2N=N1.NC1[S:60][N:59]=[C:58]([CH2:61][C:62]([OH:64])=[O:63])N=1>ClCCl>[CH2:38]([O:64][C:62](=[O: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)[CH:37]=[CH2:36]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 18689696HCID 18689696, compoundHCID 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 57920167(5-{(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoylamino}-[1,2,4]thiadiazol-3-yl)-acetic acid allyl esterYield 70%

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, 132 mg, 0.41 mmol) in dichloromethane (2.00 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (91 mg, 0.47 mmol) and 1-hydroxybenzotriazole (62 mg, 0.46 mmol). The resulting solution was stirred for 5 min before (5-amino-[1,2,4]thiadiazol-3-yl)-acetic acid ally ester hydrochloride (1:1) (100 mg, 0.50 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) which afforded (5-{(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoylamino}-[1,2,4]thiadiazol-3-yl)-acetic acid allyl ester (145 mg, 70%) as a light yellow solid: HR-ES-MS m/z calculated for C23H25ClN4O5S [M+H]+ 505.1307, observed 505.1306; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.91 (d, J=6.4 Hz, 3H), 0.95 (d, J=6.4 Hz, 3H), 1.36-1.57 (m, 1H), 1.58-1.76 (m, 1H), 1.77-1.96 (m, 1H), 3.97 (s, 2H), 4.30 (d, J=18.0 Hz, 1H), 4.50 (d, J=18.0 Hz, 1H), 4.59 (d, J=5.6 Hz, 2H), 4.83 (s, 1H), 5.01 (dd, J=11.3, 5.6 Hz, 1H), 5.16-5.35 (m, 2H), 5.77-6.01 (m, 1H), 7.37 (ddd, J=8.0, 1.5 Hz, 1H), 7.47 (td, J=8.0, 1.5 Hz, 1H), 7.54 (dd, J=8.0, 1.5 Hz, 1H), 7.66 (dd, J=8.0, 1.5 Hz, 1H), 13.43 (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) which

Sources & evidence

ORD record
ord-e4751ba8dbd04675bc6bda1d537a4778
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

Loading…