Diisopropylethylamine → tert-butyl 3-(3-(3-(methylthio)-1-phenyl-1H-indazol-6-yl)ureido)pyrrolidine-1-carboxylate

HRID 68682Notes

Reaction equation

HRID 68682 reaction equation
Cl[C:2]([O:5]C(=O)OC(Cl)(Cl)Cl)(Cl)Cl.[CH3:13][S:14][C:15]1[C:23]2[C:18](=[CH:19][C:20]([NH2:24])=[CH:21][CH:22]=2)[N:17]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[N:16]=1.CCN(C(C)C)C(C)C.[NH2:40][CH:41]1[CH2:45][CH2:44][N:43]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:42]1>ClCCl>[CH3:13][S:14][C:15]1[C:23]2[C:18](=[CH:19][C:20]([NH:24][C:2](=[O:5])[NH:40][CH:41]3[CH2:45][CH2:44][N:43]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:42]3)=[CH:21][CH:22]=2)[N:17]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[N:16]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 27563701-Boc-3-aminopyrrolidineHCID 498399773-(methylthio)-1-phenyl-1H-indazol-6-amine

Product 1

HCID 67448228tert-butyl 3-(3-(3-(methylthio)-1-phenyl-1H-indazol-6-yl)ureido)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

Into a 50-mL 3-necked round-bottom flask, was placed a solution of bis(trichloromethyl)carbonate (200 mg, 0.67 mmol) in dichloromethane (3 mL). To the resulting mixture was then added a mixture of 3-(methylthio)-1-phenyl-1H-indazol-6-amine (500 mg, 1.96 mmol, 1.00 equiv) and DIEA (560 mg, 4.33 mmol, 2.21 equiv) in dichloromethane (2 mL) dropwise with stirring at 0° C. in 30 min. The resulting solution was stirred for 3 h at 15° C. The resulting mixture was added to a solution of tert-butyl 3-aminopyrrolidine-1-carboxylate (440 mg, 2.37 mmol, 1.21 equiv) in dichloromethane (3 mL) dropwise with stirring at 15° C. in 15 min. The resulting solution stirred for an additional 4 h at 15° C. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate:petroleum ether (1:4˜1:3) to yield tert-butyl 3-(3-(3-(methylthio)-1-phenyl-1H-indazol-6-yl)ureido)pyrrolidine-1-carboxylate as a white solid. MS: 468 (MH+).

Workup

  1. customInto a 50-mL 3-necked round-bottom flask, was placed
  2. additionTo the resulting mixture was then added
  3. stirringThe resulting solution was stirred for 3 h at 15° C
  4. stirringwith stirring at 15° C. in 15 min
  5. stirringThe resulting solution stirred for an additional 4 h at 15° C
  6. concentrationThe resulting mixture was concentrated under vacuum

Sources & evidence

ORD record
ord-64c5866a5fbc4a87a594f9858b5d8e92
Source dataset
uspto-grants-2014_09
Patent number
US08822447B2

Reaction notes

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