1-Hydroxybenzotriazole → 2-(4-{[5-chloro-2-{[(1,5-dimethyl-1H-pyrazol-3-yl)carbonyl]amino}-4-(trifluoromethyl)phenyl]amino}phenyl)ethyl (4-methylphenyl)sulfonylcarbamate

HRID 2077746Notes

Reaction equation

HRID 2077746 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12](=[O:35])[O:13][CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([NH:22][C:23]3[CH:28]=[C:27]([Cl:29])[C:26]([C:30]([F:33])([F:32])[F:31])=[CH:25][C:24]=3[NH2:34])=[CH:18][CH:17]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[CH3:36][N:37]1[C:41]([CH3:42])=[CH:40][C:39]([C:43](O)=[O:44])=[N:38]1.C(N(CC)C(C)C)(C)C.C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl.CN(C=O)C>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([NH:11][C:12](=[O:35])[O:13][CH2:14][CH2:15][C:16]2[CH:17]=[CH:18][C:19]([NH:22][C:23]3[CH:28]=[C:27]([Cl:29])[C:26]([C:30]([F:33])([F:31])[F:32])=[CH:25][C:24]=3[NH:34][C:43]([C:39]3[CH:40]=[C:41]([CH3:42])[N:37]([CH3:36])[N:38]=3)=[O:44])=[CH:20][CH:21]=2)(=[O:9])=[O:10])=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 5877571,5-dimethyl-1H-pyrazole-3-carboxylic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 866115012-(4-{[2-Amino-5-chloro-4-(trifluoromethyl)phenyl]amino}phenyl)ethyl (4-methylphenyl)sulfonylcarbamate

Product 1

HCID 865856292-(4-{[5-chloro-2-{[(1,5-dimethyl-1H-pyrazol-3-yl)carbonyl]amino}-4-(trifluoromethyl)phenyl]amino}phenyl)ethyl (4-methylphenyl)sulfonylcarbamateYield 59%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 2-(4-{[2-amino-5-chloro-4-(trifluoromethyl)phenyl]amino}phenyl)ethyl (4-methylphenyl)sulfonylcarbamate (step 2, 200 mg, 0.379 mmol) in dichloromethane (1.7 ml) was added a solution of 1,5-dimethyl-1H-pyrazole-3-carboxylic acid (63.8 mg, 0.455 mmol) and N,N-diisopropylethylamine (118 mg, 0.909 mmol) in dichloromethane (1.7 ml), then to the mixture was added a solution of HOBt (61.5 mg, 0.455 mmol) and HBTU (431 mg, 1.14 mmol) in DMF (2.5 ml), and the mixture was stirred at room temperature for 20 h. The mixture was quenched with water (100 ml). The whole was extracted with ethyl acetate (100 ml×3). The combined organic layer was washed with water (100 ml×3), brine (50 ml), dried (MgSO4), and concentrated. Purification by PTLC eluting with hexane/ethyl acetate (1:1) to afford 145 mg (59%) of the title compound as a red solid.

Workup

  1. customThe mixture was quenched with water (100 ml)
  2. extractionThe whole was extracted with ethyl acetate (100 ml×3)
  3. washThe combined organic layer was washed with water (100 ml×3), brine (50 ml)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customPurification by PTLC
  7. washeluting with hexane/ethyl acetate (1:1)

Sources & evidence

ORD record
ord-2ad806582e304418a0b8522b8e0823e1
Source dataset
uspto-grants-2011_04
Patent number
US07928119B2

Reaction notes

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