Diisopropylethylamine → HCID 86585146, compound

HRID 393034Notes

Reaction equation

HRID 393034 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([O-:10])=O)[CH:5]=[CH:4][C:3]=1[C:11]([O:13][CH3:14])=[O:12].CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.[NH2:42][CH2:43][C:44]1[CH:52]=[CH:51][CH:50]=[C:49]2[C:45]=1[CH:46]=[N:47][N:48]2[CH:53]1[CH2:58][CH2:57][CH2:56][CH2:55][O:54]1.C(N(C(C)C)CC)(C)C>ClCCl>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([NH:42][CH2:43][C:44]2[CH:52]=[CH:51][CH:50]=[C:49]3[C:45]=2[CH:46]=[N:47][N:48]3[CH:53]2[CH2:58][CH2:57][CH2:56][CH2:55][O:54]2)=[O:10])[CH:5]=[CH:4][C:3]=1[C:11]([O:13][CH3:14])=[O:12]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 212765331,4-Benzenedicarboxylic acid, 2-chloro-, 1-methyl esterHCID 226611964-aminomethyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

Product 1

HCID 86585146HCID 86585146, compoundYield 55.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

2-Chloro-1,4-benzenedicarboxylic acid, 1-methyl ester (Example 1; 84.3 mg, 0.393 mmol) was suspended in dichloromethane (1.5 mL) and the mixture was cooled to 0° C. BOP reagent (191 mg, 0.432 mmol) was added in one portion, followed by 4-aminomethyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (Example 12; 91 mg, 0.393 mmol) with a 2×0.25 mL wash of dichloromethane. Diisopropylethylamine (0.21 g, 1.62 mmol) was added over 1 min at ˜0° C. The mixture was stirred at ˜0° C. for 30 min and then at room temperature for 3.5 h. The mixture was concentrated to remove dichloromethane, and ethyl acetate (60 mL) was added. The solution was washed with 1 M HCl, sodium hydrogen carbonate solution, and brine (10 mL each), then dried (MgSO4), filtered, and concentrated. Ethyl acetate/petroleum ether was added and the insoluble material was filtered off to give 2-chloro-4-[[[[1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-yl]methyl]amino]carbonyl]benzoic acid, methyl ester (93 mg, 55%) as a white solid.

Workup

  1. washwash of dichloromethane
  2. waitat room temperature for 3.5 h
  3. concentrationThe mixture was concentrated
  4. customto remove dichloromethane, and ethyl acetate (60 mL)
  5. additionwas added
  6. washThe solution was washed with 1 M HCl, sodium hydrogen carbonate solution, and brine (10 mL each)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. additionEthyl acetate/petroleum ether was added
  11. filtrationthe insoluble material was filtered off

Sources & evidence

ORD record
ord-df196e890bc74b679097115ae82d00e3
Source dataset
uspto-grants-2004_10
Patent number
US06803384B2

Reaction notes

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