Triethylamine → 4-(2-(5-bromo-2-fluorophenyl)pteridin-4-ylamino)-N-(3-(2-oxopyrrolidin-1-yl)propyl)nicotinamide

HRID 928267

Reaction equation

HRID 928267 reaction equation
C([N:3](CC)CC)C.[Br:8][C:9]1[CH:10]=[CH:11][C:12]([F:35])=[C:13]([C:15]2[N:24]=[C:23]([NH:25][C:26]3[C:31]([C:32]([OH:34])=O)=[CH:30][N:29]=[CH:28][CH:27]=3)[C:22]3[C:17](=[N:18][CH:19]=[CH:20][N:21]=3)[N:16]=2)[CH:14]=1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.N[CH:70]([CH3:78])[CH2:71][N:72]1[CH2:76][CH2:75][CH2:74][C:73]1=[O:77]>C(Cl)Cl>[Br:8][C:9]1[CH:10]=[CH:11][C:12]([F:35])=[C:13]([C:15]2[N:24]=[C:23]([NH:25][C:26]3[C:31]([C:32]([NH:3][CH2:78][CH2:70][CH2:71][N:72]4[CH2:76][CH2:75][CH2:74][C:73]4=[O:77])=[O:34])=[CH:30][N:29]=[CH:28][CH:27]=3)[C:22]3[C:17](=[N:18][CH:19]=[CH:20][N:21]=3)[N:16]=2)[CH:14]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 167870031-(2-Aminopropyl)-2-pyrrolidinoneHCID 577423744-[[2-(5-Bromo-2-fluorophenyl)pteridin-4-yl]amino]nicotinic Acid

Product 1

HCID 119557904-(2-(5-bromo-2-fluorophenyl)pteridin-4-ylamino)-N-(3-(2-oxopyrrolidin-1-yl)propyl)nicotinamideYield 30.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Triethylamine (140 μL, 1.00 mmol) was slowly added to a solution of 4-[[2-(5-bromo-2-fluorophenyl)pteridin-4-yl]amino]nicotinic acid 16 (150 mg, 0.340 mmol), PyBOP (0.350 mg, 0.68 mmol), and 1-(β-aminopropyl)pyrrolidinone (97 mg, 0.68 mmol) in CH2Cl2 (10 mL). After 15 min at room temperature, the reaction mixture was evaporated and the residue purified by column chromatography (AcOEt/CH2Cl2, 2:1+1% triethylamine to AcOEt/CH2Cl2/MeOH, 7:2:1+1% triethylamine). The yellow powder was recrystallized from EtOH to give 58 mg of the title product 21 as yellow prisms (LCMS analysis).

Workup

  1. customthe reaction mixture was evaporated
  2. customthe residue purified by column chromatography (AcOEt/CH2Cl2, 2:1+1% triethylamine to AcOEt/CH2Cl2/MeOH, 7:2:1+1% triethylamine)
  3. customThe yellow powder was recrystallized from EtOH

Sources & evidence

ORD record
ord-702c0055a4154d8086e2321a7aa40a1f
Source dataset
uspto-grants-2016_03
Patent number
US09290502B2

Linked notes

Loading…