3-Aminopyridine → 5-[2-Methyl-5-(morpholine-4-sulfonyl)-phenyl]-N*3*-pyridin-3-yl-pyrazine-2,3-diamine

HRID 81470Notes

Reaction equation

HRID 81470 reaction equation
[H-].[Na+].[N:3]1[CH:8]=[CH:7][CH:6]=[C:5]([NH2:9])[CH:4]=1.Cl[C:11]1[C:12]([NH2:33])=[N:13][CH:14]=[C:15]([C:17]2[CH:22]=[C:21]([S:23]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)(=[O:25])=[O:24])[CH:20]=[CH:19][C:18]=2[CH3:32])[N:16]=1>C1COCC1>[CH3:32][C:18]1[CH:19]=[CH:20][C:21]([S:23]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)(=[O:25])=[O:24])=[CH:22][C:17]=1[C:15]1[N:16]=[C:11]([NH:9][C:5]2[CH:4]=[N:3][CH:8]=[CH:7][CH:6]=2)[C:12]([NH2:33])=[N:13][CH:14]=1

Participants

5

Reactant 3

HCID 100093-AminopyridineHCID 24758Sodium hydride2×HCID 866345543-Chloro-5-[2-methyl-5-(morpholine-4-sulfonyl)-phenyl]-pyrazin-2-ylamine2×

Product 1

HCID 578757795-[2-Methyl-5-(morpholine-4-sulfonyl)-phenyl]-N*3*-pyridin-3-yl-pyrazine-2,3-diamine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of NaH (60% dispersion in oil) (12 mg, 0.298 mmol) is stirred in THF (3 ml). Pyridine-3-ylamine (28 mg, 0.293 mmol) is added and gas evolved. Once all gas production is stopped 3-Chloro-5-[2-methyl-5-(morpholine-4-sulfonyl)-phenyl]-pyrazin-2-ylamine (Intermediate M) (100 mg, 0.271 mmol) in THF (3 ml) is added. The reaction mixture is microwaved at 120° C. for 10 minutes. More NaH (60%) (33 mg, 0.813 mmol) is added to the reaction mixture and the sample is microwaved at 120° C. for 40 minutes. The reaction is quenched with water (100 ml) and evaporated to dryness in vacuo. The brown residue is purified by reverse phase column chromatography to yield the title compound as a brown glass. 1H NMR (400 MHz, DMSO-6) δ 9.14 (1H, d), 8.99 (1H, s), 8.38-8.33 (3H, m), 7.81 (1H, s), 7.70 (1H, d), 7.66-7.60 (5H, m), 3.64 (4H, t), 2.88 (4H, t), 2.54 (3H, s); MS m/z 427 [M+H]+

Workup

  1. additionis added
  2. customThe reaction mixture is microwaved at 120° C. for 10 minutes
  3. customthe sample is microwaved at 120° C. for 40 minutes
  4. customThe reaction is quenched with water (100 ml)
  5. customevaporated to dryness in vacuo
  6. customThe brown residue is purified by reverse phase column chromatography

Sources & evidence

ORD record
ord-7e6f2962ca0041ad846e2133aa93649f
Source dataset
uspto-grants-2014_09
Patent number
US08846687B2

Reaction notes

Loading…