Hydrochloric Acid → N6-(2-Chloro-6-methyl-4-pyrimidinyl)-2-methyl-4,6-quinolinediamine

HRID 1432202

Reaction equation

HRID 1432202 reaction equation
[CH3:1][C:2]1[CH:11]=[C:10]([NH2:12])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([NH2:13])[CH:8]=2)[N:3]=1.[Cl:14][C:15]1[N:20]=[C:19](Cl)[CH:18]=[C:17]([CH3:22])[N:16]=1.Cl>C(O)CO.O>[Cl:14][C:15]1[N:20]=[C:19]([NH:13][C:7]2[CH:8]=[C:9]3[C:4](=[CH:5][CH:6]=2)[N:3]=[C:2]([CH3:1])[CH:11]=[C:10]3[NH2:12])[CH:18]=[C:17]([CH3:22])[N:16]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 794712,4-Dichloro-6-methylpyrimidineHCID 2239952-Methylquinoline-4,6-diamine

Product 1

HCID 57636160N6-(2-Chloro-6-methyl-4-pyrimidinyl)-2-methyl-4,6-quinolinediamineYield 27%

Reagents, catalysts & solvents 2

HCID 174Ethylene GlycolSolventHCID 962WaterSolvent

Procedure

Diaminoquinoline 7 (72.0 g, 0.416 mol) and 2,4-dichloro-6-methylpyrimidine (8) (67.8 g, 0.416 mol) were suspended in ethylene glycol (1 L). Addition of 37% HCl (35 mL, 0.43 mol) resulted in a yellow solution which was heated to and held at 50° C. for 4.5 h. The mixture was diluted with chilled water (1 L) which resulted in a thick white paste-like precipitate and the mixture was filtered through Celite. The Celite and solid containing the product and bis-substituted by-product was slurried in water (4 L) and the Celite and insoluble by-product were removed by filtration. The filtrate pH was adjusted to 14 using 1N aqueous NaOH (1 L) resulting in precipitation of product which was removed by filtration. The damp product was transferred to a rotovap flask and dried in vacuo by azeotropic water removal with toluene (3×1.5 L). Product 9 was obtained as an off-white solid (33.4 g, 27% yield; Notebook reference A134-137). Another batch of 9 (7.4 g, 17% yield; Notebook reference A134-134) was similarly obtained by reaction of 7 (25.0 g, 0.144 mol) and recovery as above; MS [M+1]=300, 302; 13C NMR (DMSO) δ 167.51, 162.58, 159.22, 157.61, 151.05, 145.99, 133.17, 128.96, 125.39, 117.38, 114.23, 102.45, 102.26, 24.68, 23.19.

Workup

  1. customresulted in a yellow solution which
  2. temperaturewas heated to and
  3. customresulted in a thick white paste-like precipitate
  4. filtrationthe mixture was filtered through Celite
  5. additionThe Celite and solid containing the product and bis-substituted by-product
  6. customthe Celite and insoluble by-product were removed by filtration
  7. customresulting in precipitation of product which
  8. customwas removed by filtration
  9. customThe damp product was transferred to a rotovap flask
  10. dry with materialdried in vacuo by azeotropic water removal with toluene (3×1.5 L)

Sources & evidence

ORD record
ord-c03830271f61434c8f95e19948ae8e8c
Source dataset
uspto-grants-2009_11
Patent number
US07612080B2

Linked notes

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