Anisole → N2-(2,6-dimorpholinopyridin-4-yl)-N4-(1H-indazol-4-yl)pyrimidine-2,4-diamine

HRID 2237408Notes

Reaction equation

HRID 2237408 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[C:10]3[CH:11]=[N:12][N:13](CC4C=CC(OC)=CC=4)[C:14]=3[CH:15]=[CH:16][CH:17]=2)[CH:5]=[CH:4][N:3]=1.[O:27]1[CH2:32][CH2:31][N:30]([C:33]2[CH:38]=[C:37]([NH2:39])[CH:36]=[C:35]([N:40]3[CH2:45][CH2:44][O:43][CH2:42][CH2:41]3)[N:34]=2)[CH2:29][CH2:28]1.C1(OC)C=CC=CC=1>>[O:27]1[CH2:32][CH2:31][N:30]([C:33]2[CH:38]=[C:37]([NH:39][C:2]3[N:7]=[C:6]([NH:8][C:9]4[CH:17]=[CH:16][CH:15]=[C:14]5[C:10]=4[CH:11]=[N:12][NH:13]5)[CH:5]=[CH:4][N:3]=3)[CH:36]=[C:35]([N:40]3[CH2:41][CH2:42][O:43][CH2:44][CH2:45]3)[N:34]=2)[CH2:29][CH2:28]1

Participants

4

Reactant 3

HCID 7519AnisoleHCID 575713742,6-Dimorpholin-4-ylpyridin-4-amineHCID 86626272N-(2-chloropyrimidin-4-yl)-1-(4-methoxybenzyl)-1H-indazol-4-amine

Product 1

HCID 25138375N2-(2,6-dimorpholinopyridin-4-yl)-N4-(1H-indazol-4-yl)pyrimidine-2,4-diamineYield 34.5%

Conditions

Temperature
130 °C

Procedure

N-(2-chloropyrimidin-4-yl)-1-(4-methoxybenzyl)-1H-indazol-4-amine (400 mg, 1.09 mmol) and 2,6-dimorpholinopyridin-4-amine (289 mg, 1.09 mmol) were reacted according to procedure of Example 1. After filtration of the solids and evaporation of the solvents, the resulting gum was dissolved in TFA (8.2 mL) and anisole (0.594 mL, 5.47 mmol) and sealed into a microwave tube. The reaction was heated to 130° C. over a period of 30 minutes in a Personal Chemistry EMRYS™ Optimizer EXP microwave synthesisor. The reaction mixture was concentrated to dryness, diluted with dichloromethane (20 ml), washed with water (20 ml), brine (20 ml), dried over magnesium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 5% methanol in dichloromethane. The solvent was evaporated to dryness. The resulting solid was triturated with diethyl ether/petroleum ether (1/1), collected by filtration and dried under vacuum to give N2-(2,6-dimorpholinopyridin-4-yl)-N4-(1H-indazol-4-yl)pyrimidine-2,4-diamine (178 mg, 34.4%) as a pale beige solid. NMR Spectrum: (DMSOd6) 3.17 (bs, 8H), 3.61 (bs, 8H), 6.47 (s, 1H), 6.59 (s, 2H), 7.22 (s, 1H), 7.27 (s, 1H), 7.79 (s, 1H), 8.12 (s, 1H), 8.21 (s, 1H), 9.16 (s, 1H), 9.46 (s, 1H), 13.06 (s, 1H); Mass spectrum: MH+ 474.

Workup

  1. filtrationAfter filtration of the solids and evaporation of the solvents
  2. dissolutionthe resulting gum was dissolved in TFA (8.2 mL)
  3. concentrationThe reaction mixture was concentrated to dryness
  4. additiondiluted with dichloromethane (20 ml)
  5. washwashed with water (20 ml), brine (20 ml)
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography on silica gel eluting with 0 to 5% methanol in dichloromethane
  9. customThe solvent was evaporated to dryness
  10. customThe resulting solid was triturated with diethyl ether/petroleum ether (1/1)
  11. filtrationcollected by filtration
  12. customdried under vacuum

Sources & evidence

ORD record
ord-9a14776d7b3f4a5e82b1aa18f3148f73
Source dataset
uspto-grants-2010_05
Patent number
US07718653B2

Reaction notes

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