Triethylamine → 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-N-(4-fluorobenzyl)pyrimidine-5-formamide

HRID 2200877Notes

Reaction equation

HRID 2200877 reaction equation
[CH:1]12[CH2:6][CH:5]1[CH2:4][N:3]([C:7]1[N:12]=[C:11]([NH:13][CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([Cl:23])[CH:16]=3)[C:10]([C:24](O)=[O:25])=[CH:9][N:8]=1)[CH2:2]2.[F:27][C:28]1[CH:35]=[CH:34][C:31]([CH2:32][NH2:33])=[CH:30][CH:29]=1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1.O>[CH:1]12[CH2:6][CH:5]1[CH2:4][N:3]([C:7]1[N:12]=[C:11]([NH:13][CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([Cl:23])[CH:16]=3)[C:10]([C:24]([NH:33][CH2:32][C:31]3[CH:34]=[CH:35][C:28]([F:27])=[CH:29][CH:30]=3)=[O:25])=[CH:9][N:8]=1)[CH2:2]2

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 673264-FluorobenzylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 1176225452-(3-Azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)pyrimidine-5-carboxylic acid

Product 1

HCID 732145442-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-N-(4-fluorobenzyl)pyrimidine-5-formamideYield 16%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

In THF (10 mL) were dissolved 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)pyrimidine-5-carboxylic acid (150 mg, 0.40 mmol), 4-fluorobenzylamine (56 mg, 0.45 mmol) and triethylamine (101 mg, 1 mmol). The reaction mixture was cooled in an ice bath and HATU (266 mg, 0.70 mmol) was added. The reaction was conducted at ambient temperature for 4 h. The reaction mixture was diluted with water and extracted with DCM. The organic phase was dried, concentrated, and purified by silica gel column chromatography (DCM/methanol=20/1) to give 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-N-(4-fluorobenzyl) pyrimidine-5-formamide (30 mg, 16% yield).

Workup

  1. temperatureThe reaction mixture was cooled in an ice bath
  2. extractionextracted with DCM
  3. customThe organic phase was dried
  4. concentrationconcentrated
  5. custompurified by silica gel column chromatography (DCM/methanol=20/1)

Sources & evidence

ORD record
ord-330fbb84850a486e82beb902147d0d73
Source dataset
uspto-grants-2016_06
Patent number
US09359371B2

Reaction notes

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