1,3-Dibromopropane → Tert-butyl 3-(6-(6-(4-(3-bromopropoxy)benzylamino)-2-(2,2,2-trifluoroethoxy)pyrimidin-4-ylamino)nicotinamido)-2,2-dimethylpropylcarbamate

HRID 469276Notes

Reaction equation

HRID 469276 reaction equation
[OH:1][C:2]1[CH:44]=[CH:43][C:5]([CH2:6][NH:7][C:8]2[N:13]=[C:12]([O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[N:11]=[C:10]([NH:20][C:21]3[CH:42]=[CH:41][C:24]([C:25]([NH:27][CH2:28][C:29]([CH3:40])([CH3:39])[CH2:30][NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:26])=[CH:23][N:22]=3)[CH:9]=2)=[CH:4][CH:3]=1.[Br:45][CH2:46][CH2:47][CH2:48]Br.C([O-])([O-])=O.[K+].[K+]>CC(C)=O.CCOC(C)=O>[Br:45][CH2:46][CH2:47][CH2:48][O:1][C:2]1[CH:44]=[CH:43][C:5]([CH2:6][NH:7][C:8]2[N:13]=[C:12]([O:14][CH2:15][C:16]([F:17])([F:18])[F:19])[N:11]=[C:10]([NH:20][C:21]3[CH:42]=[CH:41][C:24]([C:25]([NH:27][CH2:28][C:29]([CH3:39])([CH3:40])[CH2:30][NH:31][C:32](=[O:38])[O:33][C:34]([CH3:35])([CH3:36])[CH3:37])=[O:26])=[CH:23][N:22]=3)[CH:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 80011,3-DibromopropaneHCID 11430Potassium CarbonateHCID 86679318Tert-butyl 3-(6-(6-(4-hydroxybenzylamino)-2-(2,2,2-trifluoroethoxy)pyrimidin-4-ylamino)nicotinamido)-2,2-dimethylpropylcarbamate

Product 1

HCID 86679320Tert-butyl 3-(6-(6-(4-(3-bromopropoxy)benzylamino)-2-(2,2,2-trifluoroethoxy)pyrimidin-4-ylamino)nicotinamido)-2,2-dimethylpropylcarbamateYield 30.7%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspenssion of tert-butyl (3-(6-((6-((4-hydroxybenzyl)amino)-2-(2,2,2-trifluoroethoxy)pyrimidin-4-yl)amino)nicotinamido)-2,2-dimethylpropyl)carbamate (30 mg), 1,3-dibromopropane (14.7 mg) and K2CO3 (13.4 mg) in acetone (6 mL) was heated to reflux for 16 hours. The mixture was diluted with EtOAc (200 mL), washed with water (30 mL), brine (30 mL), dried over MgSO4 and concentrated. The residue was purified by preparative HPLC to give desired product tert-butyl 3-(6-(6-(4-(3-bromopropoxy)benzylamino)-2-(2,2,2-trifluoroethoxy)pyrimidin-4-ylamino)nicotinamido)-2,2-dimethylpropylcarbamate (11 mg).

Workup

  1. temperatureto reflux for 16 hours
  2. washwashed with water (30 mL), brine (30 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-0bae5348db8f4b2ea1d44833b6a451d4
Source dataset
uspto-grants-2014_01
Patent number
US08629150B2

Reaction notes

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