Triethylamine → 2-{2,5-Difluoro-4-[2-((1S,2R)-2-{1-[5-(methoxymethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl)ethoxy]phenyl}-N,N-dimethylacetamide

HRID 1474718Notes

Reaction equation

HRID 1474718 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH2:10][C@@H:11]2[CH2:13][C@@H:12]2[CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[C:5]([F:20])=[CH:4][C:3]=1[CH2:21][C:22]([N:24]([CH3:26])[CH3:25])=[O:23].C(N(CC)CC)C.Cl[C:35]1[N:40]=[CH:39][C:38]([CH2:41][O:42][CH3:43])=[CH:37][N:36]=1>CN(C=O)C>[F:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH2:10][C@@H:11]2[CH2:13][C@@H:12]2[CH:14]2[CH2:15][CH2:16][N:17]([C:35]3[N:40]=[CH:39][C:38]([CH2:41][O:42][CH3:43])=[CH:37][N:36]=3)[CH2:18][CH2:19]2)[C:5]([F:20])=[CH:4][C:3]=1[CH2:21][C:22]([N:24]([CH3:26])[CH3:25])=[O:23]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 867112002-(2,5-difluoro-4-{2-[(1S,2R)-2-piperidin-4 ylcyclopropyl]ethoxy}phenyl-)-N,N-dimethylacetamideHCID 867177852-chloro-5-(MethoxyMethyl)pyriMidine

Product 1

HCID 895840822-{2,5-Difluoro-4-[2-((1S,2R)-2-{1-[5-(methoxymethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl)ethoxy]phenyl}-N,N-dimethylacetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(2,5-difluoro-4-{2-[(1S,2R)-2-piperidin-4-ylcyclopropyl]ethoxy}phenyl-)-N,N-dimethylacetamide (40.0 mg, 0.109 mmol) in 1 ml anhydrous DMF at RT was added triethylamine (0.046 ml, 0.33 mmol) and 2-chloro-5-(methoxymethyl)pyrimidine (20.8 mg, 0.131 mmol). The mixture was stirred at RT for 2 hours. The mixture was filtered and purified by reverse-phase HPLC (SunFire Prep C18 OBD Sum 19×100 mm column; 35-65% acetonitrile in 0.1% formic acid in water gradient) to afford the title compound. LC/MS (m/z): 489.5 (M+H)+. Human EC50: 1.6 nM

Workup

  1. filtrationThe mixture was filtered
  2. custompurified by reverse-phase HPLC (SunFire Prep C18 OBD Sum 19×100 mm column; 35-65% acetonitrile in 0.1% formic acid in water gradient)

Sources & evidence

ORD record
ord-f5a2e542281d456eb4091266d3ba14e0
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

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