Chloride → HCID 59361984, compound

HRID 61561Notes

Reaction equation

HRID 61561 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[N:17]=[C:16]([NH:18][C:19]3[CH:20]=[C:21]4[C:25](=[CH:26][CH:27]=3)[N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[N:23]=[CH:22]4)[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:35][N:36]([CH3:40])[C:37](Cl)=[O:38].CCN(CC)CC.[Cl-]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:35][N:36]([CH3:40])[C:37](=[O:38])[NH:1][C:2]1[CH:3]=[C:4]([C:8]2[N:17]=[C:16]([NH:18][C:19]3[CH:20]=[C:21]4[C:25](=[CH:26][CH:27]=3)[N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[N:23]=[CH:22]4)[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 312Chloride2×HCID 6598Dimethylcarbamoyl Chloride2×HCID 8471Triethylamine4×HCID 66825994tert-butyl 5-(2-(3-aminophenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate

Product 1

HCID 59361984HCID 59361984, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a suspension of tert-butyl 5-(2-(3-aminophenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate (75 mg, 0.17 mmol) and dimethylcarbamic chloride (30 μL, 0.33 mmol,) in CH2Cl2 (2 mL) was added Et3N (46 μL, 0.33 mmol) and catalytic amount of DMAP. The reaction mixture was stirred at RT for 2 h after which 2 equivalents each of dimethylcarbamic chloride and Et3N were added. After 2 h of stirring another 2 equivalents of both the chloride and Et3N were added. Upon the addition of the third addition of the chloride and the Et3N the temperature was raised to 45° C. The reaction mixture was stirred for 48 h. Concentrated in vacuo and the residue was purified by flash chromatography on silica (10:1 CH2Cl2:MeOH). The product tert-butyl 5-(2-(3-(3,3-dimethylureido)phenyl)-quinazolin-4-ylamino)-1H-indazole-1-carboxylate was isolated. (62 mg, 70%)

Workup

  1. additionwere added
  2. additionwere added
  3. concentrationConcentrated in vacuo
  4. customthe residue was purified by flash chromatography on silica (10:1 CH2Cl2:MeOH)

Sources & evidence

ORD record
ord-93c1ceff18cf44bab819100b215fc613
Source dataset
uspto-grants-2016_09
Patent number
US09440961B2

Reaction notes

Loading…