Methanol → 4-(4-Amino-6-(5-chloro-1H-indol-4-ylmethyl)-(1,3,5)triazin-2-ylamino)-benzonitrile

HRID 270626Notes

Reaction equation

HRID 270626 reaction equation
CO.[NH2:3][C:4]1[N:9]=[C:8]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]#[N:18])=[CH:13][CH:12]=2)[N:7]=[C:6]([CH2:19][C:20]2[C:28]([Cl:29])=[CH:27][CH:26]=[C:25]3[C:21]=2[CH:22]=[CH:23][N:24]3S(C2C=CC(C)=CC=2)(=O)=O)[N:5]=1.C([O-])([O-])=O.[K+].[K+]>O>[NH2:3][C:4]1[N:5]=[C:6]([CH2:19][C:20]2[C:28]([Cl:29])=[CH:27][CH:26]=[C:25]3[C:21]=2[CH:22]=[CH:23][NH:24]3)[N:7]=[C:8]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]#[N:18])=[CH:13][CH:12]=2)[N:9]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 11430Potassium CarbonateHCID 22281693HCID 22281693, compound

Product 1

HCID 4485334-(4-Amino-6-(5-chloro-1H-indol-4-ylmethyl)-(1,3,5)triazin-2-ylamino)-benzonitrileYield 45%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

Methanol (120 ml) was added to a mixture of intermediate (5) (2.35 g) and K2CO3 (9.19 g) in water (40 ml). The resulting reaction mixture was stirred and refluxed for 19 hours under argon. Water (120 ml) was added, the precipitate was filtered off and purified by column chromatography over silica gel (eluent: DCM/2-propanone 90/10). Two desired fractions were collected and their solvent was evaporated. The first fraction group was slurried in ACN, cooled, filtered off and dried, yielding 0.75 g (45%, white solid) of 4-[[4-amino-6-[(5-chloro-1H-indol-4-yl)methyl]-1,3,5-triazin-2-yl]amino]benzonitrile (compound 8, mp. 267-268° C.). The second column fraction group yielded 0.15 g of 4-[[4-amino-6-[(5-chloro-1H-indol-4-yl)methyl]-1,3,5-triazin-2-yl]amino]benzamide (compound 9). After 24 hours at RT the aqueous filtrate was filtered to give 0.25 g of compound (9). The two fractions of compound 9 were combined, dissolved in 500 ml of refluxing methanol, hot filtered, the filtrate concentrated to 50 ml, cooled and filtered, then dried, yielding 0.25 g (14%) of 4-[[4-amino-6-[(5-chloro-1H-indol-4-yl)methyl]-1,3,5-triazin-2-yl]amino]benzamide (compound 9, mp. 204-205° C.).

Workup

  1. customThe resulting reaction mixture
  2. temperaturerefluxed for 19 hours under argon
  3. filtrationthe precipitate was filtered off
  4. custompurified by column chromatography over silica gel (eluent: DCM/2-propanone 90/10)
  5. customTwo desired fractions were collected
  6. customtheir solvent was evaporated
  7. temperaturecooled
  8. filtrationfiltered off
  9. customdried

Sources & evidence

ORD record
ord-664c7129180849aabf0a1b1f6129e5a6
Source dataset
uspto-grants-2008_11
Patent number
US07449575B2

Reaction notes

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