Triethylamine → HCID 67272458, compound

HRID 1696553Notes

Reaction equation

HRID 1696553 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:15]=2[Cl:21])=[O:12])[N:7]([C:22]2[CH:31]=[C:30]3[C:25]([CH2:26][C@@H:27]([C:38](OC)=[O:39])[N:28](C(=O)C(F)(F)F)[CH2:29]3)=[CH:24][CH:23]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.CN.[CH2:45]([N:47](CC)CC)C.[CH3:52][C:53]([O:56][C:57]([O:59]C(OC(C)(C)C)=O)=O)([CH3:55])[CH3:54]>CO.O>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:15]=2[Cl:21])=[O:12])[N:7]([C:22]2[CH:31]=[C:30]3[C:25]([CH2:26][C@@H:27]([C:38](=[O:39])[NH:47][CH3:45])[N:28]([C:57]([O:56][C:53]([CH3:55])([CH3:54])[CH3:52])=[O:59])[CH2:29]3)=[CH:24][CH:23]=2)[N:6]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 90495Di-tert-butyl dicarbonateHCID 6364545Methylamine hydrochlorideHCID 58851455HCID 58851455, compound

Product 1

HCID 67272458HCID 67272458, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A solution of (3S)-methyl 7-(3-t-butyl-5-(3-(2,3-dichlorophenyl)ureido)-1H-pyrazol-1-yl)-2-(2,2,2-trifluoro-acetyl)-1,2,3,4-tetrahydroiso-quinoline-3-carboxylate from Example A42 (0.153 g, 0.250 mmol), methylamine hydrochloride (1.000 g, 14.8 mmol) and triethylamine (2.05 mL, 1.49 g, 14.7 mmol) in MeOH (5 mL) was stirred at 60° C. for 24 h. H2O was added (50 mL) and the mixture was extracted with CH2Cl2 (3×50 mL), dried (MgSO4) and concentrated. The residue was redissolved in CH2Cl2 (5 mL). Boc anhydride (0.055 g, 0.250 mmol) was added and the solution was stirred at RT for 30 min. The solvent was evaporated and the residue was purified by column chromatography to yield (3S)-t-butyl 7-(3-t-butyl-5-(3-(2,3-dichlorophenyl)ureido)-1H-pyrazol-1-yl)-3-(methyl-carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (52 mg, 34% yield) as a white solid. 1H NMR (400 MHz, acetone-d6) shows rotameric mixture. MS (EI) m/z: 615.2 (M+H+).

Workup

  1. customwas stirred at 60° C. for 24 h
  2. extractionthe mixture was extracted with CH2Cl2 (3×50 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. dissolutionThe residue was redissolved in CH2Cl2 (5 mL)
  6. customThe solvent was evaporated
  7. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-637949e91920457fb47f9da37ce5cc20
Source dataset
uspto-grants-2012_04
Patent number
US08163756B2

Reaction notes

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