1,2-Dichloroethane → HCID 10459445, compound

HRID 2376210Notes

Reaction equation

HRID 2376210 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)=[CH:12][C:11]([CH2:21][CH:22]([C:26]3[CH:27]=[C:28](C)[CH:29]=[CH:30][CH:31]=3)[C:23](O)=[O:24])=[N:10]2)=[CH:5][CH:4]=1.Cl[C:34]1C=C(C2N(C3C=CC(OC)=CC=3)N=C(CC(C3C=C(C)C=CC=3)C(O)=O)C=2)C=CC=1Cl.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.Cl.[NH2:81][C@@H:82]1[CH2:87][CH2:86][CH2:85][CH2:84][C@H:83]1[OH:88].CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[OH:88][CH:83]1[CH2:84][CH2:85][CH2:86][CH2:87][CH:82]1[NH:81][C:23](=[O:24])[CH:22]([C:26]1[CH:27]=[C:28]([CH3:34])[CH:29]=[CH:30][CH:31]=1)[CH2:21][C:11]1[CH:12]=[C:13]([C:14]2[CH:15]=[CH:16][C:17]([CH3:20])=[CH:18][CH:19]=2)[N:9]([C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)[N:10]=1

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 10096710HCID 10096710, compoundHCID 12228412Cyclohexanol, 2-amino-, hydrochloride (1:1), (1R,2R)-HCID 22171037HCID 22171037, compound

Product 1

HCID 10459445HCID 10459445, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-[1-(4-methoxy-phenyl)-5-p-tolyl-1H-pyrazol-3-yl]-2-m-tolyl-propionic acid. (product of Method 2) (100 mg, 0.23 mmol), EDC (65 mg, 0.35 mmol), and HOBT (46 mg, 0.34 mmol) in DMF (4.0 mL) was added trans-2-aminocyclohexanol hydrochloride (52 mg, 0.34 mmol) and DIEA (0.20 mL, 1.2 mmol). The reaction mixture was stirred for 24 h, diluted with EtOAc, and washed with 1.0 N NaOH (2×25 mL), water (1×25 mL), 5% formic acid (2×25 mL), water (1×25 mL) and brine (1×25 mL). The organic layer was dried (Na2SO4) and the solvent was removed under reduced pressure. Reversed-phase HPLC afforded 40 mg (33%) of N-(2-hydroxy-cyclohexyl)-3-[1-(4-methoxy-phenyl)-5-p-tolyl-1H-pyrazol-3-yl]-2-m-tolyl-propionamide as a mixture of diastereomers. HPLC: Rt=3.17 (Method B). MS (ES+): mass calculated for C33H37N3O3, 523.28; m/z found 524.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.92-7.85 (m, 1H), 7.26-7.10 (m, 6H), 7.05-7.01 (m, 3H), 6.94-6.91 (m, 2H), 6.32 (s, 0.5H), 6.29 (s, 0.5H), 4.42 (d, J=4.7 Hz, 0.5H), 4.34 (d, J=5.4 Hz, 0.5H), 3.90 (ddd, J=5.4, 9.4, 20.3 Hz, 1H), 3.76 (s, 3H), 3.24 (m, 0.5H), 3.17 (m, 0.5H), 2.85 (m, 1H), 2.30 (s, 1.5H), 2.28 (s, 1.5H), 2.27 (s, 3H), 1.75 (m, 1H), 1.55 (m, 2H), 1.13 (m, 4H), 0.97 (m, 1H).

Workup

  1. washwashed with 1.0 N NaOH (2×25 mL), water (1×25 mL), 5% formic acid (2×25 mL), water (1×25 mL) and brine (1×25 mL)
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-5a48446d9bb54870aa042f482d3308b8
Source dataset
uspto-grants-2008_12
Patent number
US07465808B2

Reaction notes

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