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 1485656Notes

Reaction equation

HRID 1485656 reaction equation
[C:1]([O:5][C:6](=[O:44])[NH:7][CH2:8][C:9]([CH3:43])([CH3:42])[CH2:10][NH:11][C:12](=[O:41])[C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20]2[CH:25]=[C:24]([NH:26][CH2:27][C:28]3[CH:33]=[CH:32][C:31]([OH:34])=[CH:30][CH:29]=3)[N:23]=[C:22]([O:35][CH2:36][C:37]([F:40])([F:39])[F:38])[N:21]=2)=[N:15][CH:14]=1)([CH3:4])([CH3:3])[CH3:2].[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:34][C:31]1[CH:30]=[CH:29][C:28]([CH2:27][NH:26][C:24]2[N:23]=[C:22]([O:35][CH2:36][C:37]([F:38])([F:40])[F:39])[N:21]=[C:20]([NH:19][C:16]3[CH:17]=[CH:18][C:13]([C:12]([NH:11][CH2:10][C:9]([CH3:43])([CH3:42])[CH2:8][NH:7][C:6](=[O:44])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:41])=[CH:14][N:15]=3)[CH:25]=2)=[CH:33][CH:32]=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 suspension of tert-butyl(3-(6-((6-((4-hydroxybenzyl)amino)-2-(2,2,2-trifluoroethoxyl)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. temperaturewas heated
  2. temperatureto reflux for 16 hours
  3. washwashed with water (30 mL), brine (30 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-431cbfecc90e4ac1aafae716a9c7d066
Source dataset
uspto-grants-2016_08
Patent number
US09422311B2

Reaction notes

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