2,4,6-Trimethylpyridine → N-((6-amino-2,4-dimethylpyridin-3-yl)methyl)-5-((1-oxoisoquinolin-2(1H)-yl)methyl)furan-2-carboxamide

HRID 928355Notes

Reaction equation

HRID 928355 reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([CH3:18])=[CH:5][C:6]([NH:10]C(=O)OC(C)(C)C)=[N:7][C:8]=1[CH3:9].N1C(C)=CC(C)=CC=1C.[O:28]=[C:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:32]=[CH:31][N:30]1[CH2:39][C:40]1[O:44][C:43]([C:45](O)=[O:46])=[CH:42][CH:41]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1>[NH2:10][C:6]1[N:7]=[C:8]([CH3:9])[C:3]([CH2:2][NH:1][C:45]([C:43]2[O:44][C:40]([CH2:39][N:30]3[CH:31]=[CH:32][C:33]4[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=4)[C:29]3=[O:28])=[CH:41][CH:42]=2)=[O:46])=[C:4]([CH3:18])[CH:5]=1

Participants

6

Reactant 4

HCID 79532,4,6-TrimethylpyridineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22475372N-[5-(aminomethyl)-4,6-dimethyl(2-pyridyl)] (tert-butoxy)carboxamideHCID 580811625-((1-oxoisoquinolin-2(1H)-yl)methyl)furan-2-carboxylic acid

Product 1

HCID 58081186N-((6-amino-2,4-dimethylpyridin-3-yl)methyl)-5-((1-oxoisoquinolin-2(1H)-yl)methyl)furan-2-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 5-(aminomethyl)-4,6-dimethylpyridin-2-ylcarbamate (41.1 mg, 0.163 mmol) in THF (5 ml) were added collidine (0.022 ml, 0.163 mmol), 5-((1-oxoisoquinolin-2(1H)-yl)methyl)furan-2-carboxylic acid (44.0 mg, 0.163 mmol) and HATU (81.0 mg, 0.212 mmol). After stirring for 18 h at rt, all volatiles were removed in vacuo. The crude intermediate was purified by column chromatography (CombiFlash Companion, 12 g SiO2, heptane to EA), dissolved in DCM (1 ml) and TFA (1 ml), kept for 1 h at rt, and concentrated. Purification by preparative HPLC (Waters Sunfire Prep C18 OBD 5 um, 100×19 mm, A: H2O+0.1% TFA, B: MeCN+0.1% TFA, 6-36% B in 10 min, 30 ml/min, rt) afforded the title compound. 1H-NMR (DMSO-d6, 400 MHz): 2.37 (s, 3H), 4.28 (d, 2H), 5.23 (s, 2H), 6.45 (d, 1H), 6.62 (s, 1H), 6.68 (d, 1H), 7.06 (d, 1H), 7.49-7.59 (m, 4H), 7.65-7.76 (m, 2H), 8.21 (d, 1H), 8.52 (t, 1H), 13.33 (s, 1H). LCMS RtM=1.50 min, [M+H]+=403.3.

Workup

  1. customall volatiles were removed in vacuo
  2. customThe crude intermediate was purified by column chromatography (CombiFlash Companion, 12 g SiO2, heptane to EA)
  3. dissolutiondissolved in DCM (1 ml)
  4. waitTFA (1 ml), kept for 1 h at rt
  5. concentrationconcentrated
  6. customPurification by preparative HPLC (Waters Sunfire Prep C18 OBD 5 um, 100×19 mm
  7. waitA: H2O+0.1% TFA, B: MeCN+0.1% TFA, 6-36% B in 10 min

Sources & evidence

ORD record
ord-84d70544a0f24d8fb755407fe85a47f0
Source dataset
uspto-grants-2016_03
Patent number
US09290485B2

Reaction notes

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