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

HRID 1669821Notes

Reaction equation

HRID 1669821 reaction equation
[CH:1]1([C:7]2[N:11]([CH2:12][C:13]3[CH:21]=[CH:20][C:16]([C:17](O)=[O:18])=[CH:15][CH:14]=3)[N:10]=[C:9]([C:22]3[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=3)[CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(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[N:11]([CH2:12][C:13]3[CH:21]=[CH:20][C:16]([C:17]([NH:60][CH2:59][CH2:57][C:56]([O:55][CH2:53][CH3:54])=[O:61])=[O:18])=[CH:15][CH:14]=3)[N:10]=[C:9]([C:22]3[CH:27]=[CH:26][C:25]([O:28][C:29]([F:30])([F:31])[F:32])=[CH:24][CH:23]=3)[CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 673350634-({5-Cyclohexyl-3-[4-(trifluoromethoxy)phenyl]-1H-pyrazol-1-yl}methyl)benzoic acidHCID 86584061beta-Amino-alanine ethyl ester hydrochloride

Product 1

HCID 10370142ETHYL N-[4-({5-CYCLOHEXYL-3-[4-(TRIFLUOROMETHOXY)PHENYL]-1H-PYRAZOL-1-YL}METHYL)BENZOYL]-beta-ALANINATE

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 177.8 mg product from Step D Example 1, 92.0 mg EDC, 64.9 mg HOBt in 1.5 mL DMF was stirred at room temperature for 30 minutes. Diisopropylethylamine (DIEA, 84 μL) and β-amino-alanine ethyl ester hydrochloride (73.7 mg) were added and the mixture stirred for additional 16 hours. The solvent was removed under reduced pressure. Some crystalline product precipitated after dissolving the residue in 14 mL 3:2 MeCN and water with 0.1% TFA. More title compound was isolated by preparative HPLC of the filtrate 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. 1H NMR (CD3OD, 600 MHz) δ 7.84˜7.87 (m, 2H), 7.75 (d, J=8.4 Hz, 2H), 7.28 (d, J=8.3 Hz, 2H), 7.18 (d, J=8.2 Hz, 2H), 6.56 (s, 1H), 5.46 (s, 2H), 4.12 (q, J=7.1 Hz, 2H), 3.60 (t, J=6.8 Hz, 2H), 2.62 (t, J=6.8 Hz, 2H), 2.60 (tt, J=11.7 & 3.3 Hz, 1H), 1.73˜1.77 (m, 4H), 1.68˜1.71 (m, 1H), 1.37˜1.43 (m, 2H), 1.24˜1.35 (m, 3H), 1.21 (t, J=7.1 Hz, 3H). LC-MS: 2.47 min. (M+H=544.4).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customSome crystalline product precipitated
  3. dissolutionafter dissolving the residue in 14 mL 3:2 MeCN and water with 0.1% TFA

Sources & evidence

ORD record
ord-1d3ce2ebeb7a41198e1b744cdfcddce1
Source dataset
uspto-grants-2011_08
Patent number
US07989475B2

Reaction notes

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