1-Pyrrolidineethanamine → 4-[[5-Bromo 4-(4-cyano-2,6-dimethylphenoxy)-6-[(1-pyrrolidinyl)ethylamino]-2-pyrimidinyl]amino]benzonitrile hydrochloride

HRID 41370Notes

Reaction equation

HRID 41370 reaction equation
[Br:1][C:2]1[C:3]([O:18][C:19]2[C:24]([CH3:25])=[CH:23][C:22]([C:26]#[N:27])=[CH:21][C:20]=2[CH3:28])=[N:4][C:5]([NH:9][C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=2)=[N:6][C:7]=1[Cl:8].O1CCCC1.[N:34]1([CH2:39][CH2:40][NH2:41])[CH2:38][CH2:37][CH2:36][CH2:35]1.Cl.C(OCC)C>CC#N.C(Cl)Cl>[ClH:8].[Br:1][C:2]1[C:3]([O:18][C:19]2[C:24]([CH3:25])=[CH:23][C:22]([C:26]#[N:27])=[CH:21][C:20]=2[CH3:28])=[N:4][C:5]([NH:9][C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=2)=[N:6][C:7]=1[NH:41][CH2:40][CH2:39][N:34]1[CH2:38][CH2:37][CH2:36][CH2:35]1

Participants

7

Reactant 4

HCID 13441-PyrrolidineethanamineHCID 8028TetrahydrofuranHCID 10953452Ether hydrochlorideHCID 117514166-Desamino 6-Chloro Etravirine

Product 1

HCID 669342764-[[5-Bromo 4-(4-cyano-2,6-dimethylphenoxy)-6-[(1-pyrrolidinyl)ethylamino]-2-pyrimidinyl]amino]benzonitrile hydrochlorideYield 50.6%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
75 °C

Procedure

4-[[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)-6-chloro-2-pyrimidinyl]amino]benzonitrile (0.000660 mol), tetrahydrofuran (1 ml), and 1-pyrrolidineethanamine (0.00198 mol) were added to a pressure vessel. The mixture was heated at 75° C. for 16 hours. CH2Cl2 was added, and the mixture was washed with water, dried, filtered and the filtrate was evaporated. Purification using flash column chromatography eluting with 1:9 methanol:methylene chloride produced a solid which was redissolved in CH3CN. HCl/diethylether 1.0M (0.48 ml) was added, and the mixture was cooled in ice. Filtration yielded 0.19 g of 4-[[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)-6-[(1-pyrrolidinyl)ethylamino]-2-pyrimidinyl]amino]benzonitrile hydrochloride (1:1) (50.6%); mp. 208-210° C. (comp. 47).

Workup

  1. washthe mixture was washed with water
  2. customdried
  3. filtrationfiltered
  4. customthe filtrate was evaporated
  5. customPurification
  6. washeluting with 1:9 methanol
  7. custommethylene chloride produced a solid which
  8. temperaturethe mixture was cooled in ice
  9. filtrationFiltration

Sources & evidence

ORD record
ord-d371c43a01bf41698bed17a52084c589
Source dataset
uspto-grants-2013_09
Patent number
US08530655B2

Reaction notes

Loading…