Diisopropylethylamine → 1-((1S,3R)-1-Biphenyl-4-ylmethyl-3-ethoxycarbonyl-butylcarbamoyl)-1H-pyrazole-3-carboxylic acid
Reaction equation
[NH:1]1[CH:5]=[CH:4][C:3]([C:6]([OH:8])=[O:7])=[N:2]1.C(N(C(C)C)CC)(C)C.[CH2:18]([O:20][C:21](=[O:42])[C@H:22]([CH3:41])[CH2:23][C@H:24]([N:38]=[C:39]=[O:40])[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[CH:28][CH:27]=1)[CH3:19]>CN(C=O)C>[C:29]1([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:28]=[CH:27][C:26]([CH2:25][C@@H:24]([NH:38][C:39]([N:1]2[CH:5]=[CH:4][C:3]([C:6]([OH:8])=[O:7])=[N:2]2)=[O:40])[CH2:23][C@H:22]([C:21]([O:20][CH2:18][CH3:19])=[O:42])[CH3:41])=[CH:31][CH:30]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
Next, to a solution of 1H-pyrazole-3-carboxylic acid (32.2 mg, 0.287 mmol) in DMF (1 mL) is added diisopropylethylamine (0.05 mL, 0.287 mmol). After 15 min a solution of the above (2R,4S)-5-biphenyl-4-yl-4-isocyanato-2-methyl-pentanoic acid ethyl ester in DMF (1 mL) is added dropwise and the mixture is stirred at room temperature for 18 hours. The mixture is purified by preparative HPLC using a gradient of 10% MeCN to 100% MeCN (0.1% TFA). Lyophilization of the appropriate fractions furnishes the title compound. HPLC Retention time 1.5 minutes (condition A); MS 450.3 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.08 (d, J=7.07 Hz, 3H), 1.10 (t, 3H), 1.86 (t, 2H), 2.52 (m, 1H), 2.85 (m, 1H), 2.98 (m, 1H), 3.98 (q, 2H), 4.11 (m, 1H), 6.85 (d, J=2.65 Hz, 1H), 7.28 (d, J=8.08 Hz, 2H), 7.33 (t, 1H), 7.44 (t, 2H), 7.57 (d, J=8.21 Hz, 2H), 7.63 (d, J=7.33 Hz, 2H), 8.29 (d, J=2.65 Hz, 1H), 8.58 (d, J=9.22 Hz, 1H), 13.33 (s, broad, 1H).
Workup
- customThe mixture is purified by preparative HPLC
Sources & evidence
- ORD record
- ord-a5ddc49094f545f293be03e72f0b04ba
- Source dataset
- uspto-grants-2012_09
- Patent number
- US08263629B2
Reaction notes
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