1-Hydroxybenzotriazole → ETHYL N-[4-({3-CYCLOHEXYL-5-[4-(TRIFLUOROMETHOXY)PHENYL]-1H-PYRAZOL-1-YL}METHYL)BENZOYL]-beta-ALANINATE

HRID 1669828Notes

Reaction equation

HRID 1669828 reaction equation
[CH:1]1([C:7]2[CH:11]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([O:18][C:19]([F:22])([F:21])[F:20])=[CH:14][CH:13]=3)[N:9]([CH2:23][C:24]3[CH:32]=[CH:31][C:27]([C:28](O)=[O:29])=[CH:26][CH:25]=3)[N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.[CH2:53]([O:55][C:56](=[O:61])[C@H:57]([CH2:59][NH2:60])N)[CH3:54]>CN(C=O)C.C(Cl)CCl>[CH:1]1([C:7]2[CH:11]=[C:10]([C:12]3[CH:13]=[CH:14][C:15]([O:18][C:19]([F:21])([F:20])[F:22])=[CH:16][CH:17]=3)[N:9]([CH2:23][C:24]3[CH:32]=[CH:31][C:27]([C:28]([NH:60][CH2:59][CH2:57][C:56]([O:55][CH2:53][CH3:54])=[O:61])=[O:29])=[CH:26][CH:25]=3)[N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 533232474-((3-cyclohexyl-5-(4-(trifluoromethoxy)phenyl)-1H-pyrazol-1-yl)methyl)benzoic acidHCID 86584061beta-Amino-alanine ethyl ester hydrochloride

Product 1

HCID 11757129ETHYL N-[4-({3-CYCLOHEXYL-5-[4-(TRIFLUOROMETHOXY)PHENYL]-1H-PYRAZOL-1-YL}METHYL)BENZOYL]-beta-ALANINATE

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 66.7 mg product from Step A Example 6, 34.5 mg EDC, 24.3 mg HOBt in 0.5 mL DMF was stirred at room temperature for 30 minutes. DIEA (31 μL) and β-amino-alanine ethyl ester hydrochloride (27.6 mg) were added and the mixture stirred for additional 16 hours. The solvent was removed under reduced pressure. The title compound was isolated as a white solid by preparative HPLC using 60˜80% MeCN gradient over 10 minutes at 8.0 mL per minute with 0.1% TFA on a 9.4×250 mm SB-C18 Zorbax column followed by lyophilization. 1H NMR (CD3OD, 600 MHz) δ 7.68 (d, J=8.4 Hz, 2H), 7.39˜7.42 (m, 2H), 7.28 (d, J=8.1 Hz, 2H), 6.99 (d, J=8.3 Hz, 2H), 6.31 (s, 1H), 5.37 (s, 2H), 4.11 (q, J=7.1 Hz, 2H), 3.59 (t, J=6.8 Hz, 2H), 2.66 (tt, J=11.6 & 3.5 Hz, 1H), 2.61 (t, J=6.8 Hz, 2H), 1.96˜2.00 (m, 2H), 1.80˜1.84 (m, 2H), 1.71˜1.75 (m, 1H), 1.45˜1.52 (m, 2H), 1.37˜1.45 (m, 2H), 1.25˜1.33 (m, 1H), 1.21 (t, J=7.1 Hz, 3H). LC-MS: 2.44 min. (M+H=544.4).

Workup

  1. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-567dd512c7a140a3931c644756ba5049
Source dataset
uspto-grants-2011_08
Patent number
US07989475B2

Reaction notes

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