4-Chloro-6-methyl-1,3,5-triazin-2-amine → 4-(2-Fluoro-5-(1-morpholinoethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

HRID 1622015Notes

Reaction equation

HRID 1622015 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH2:9])[N:3]=1.[F:10][C:11]1[C:16](B(O)O)=[CH:15][C:14]([CH:20]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[CH3:21])=[CH:13][N:12]=1.CC(N)CC1C=CC=CC=1.OP(O)(O)=O.C([O-])(=O)C.[K+]>O.CCO>[F:10][C:11]1[C:16]([C:2]2[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH2:9])[N:3]=2)=[CH:15][C:14]([CH:20]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[CH3:21])=[CH:13][N:12]=1

Participants

7

Reactant 4

HCID 305914-Chloro-6-methyl-1,3,5-triazin-2-amineHCID 62885Benzeneethanamine, alpha-methyl-, phosphate (1:1)HCID 517044Potassium AcetateHCID 595484562-Fluoro-5-(1-morpholinoethyl)pyridin-3-ylboronic acid

Product 1

HCID 666116344-(2-Fluoro-5-(1-morpholinoethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amineYield 30.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a 20 mL microwave vial was added 4-chloro-6-methyl-1,3,5-triazin-2-amine (0.300 g, 2.075 mmol), 2-fluoro-5-(1-morpholinoethyl)pyridin-3-ylboronic acid (0.580 g, 2.283 mmol), Amphos (Aldrich) (0.073 g, 0.104 mmol), potassium acetate (Aldrich) (0.611 g, 6.23 mmol), EtOH (9 mL), and water (0.9 mL). The resulting mixture was degassed by bubbling N2 for 5 min then sealed off and microwave heated at 100° C. for 20 min. The reaction mixture was partitioned between 25% IPA in CHCl3 (1% NH4OH) (30 mL) and water (50 mL). The aqueous layer was extracted with more 25% IPA in CHCl3 (2×10 mL). The combined organic layers were dried over MgSO4 and concentrated. The crude product was purified by column chromatography (40 g, 3% MeOH in DCM) to afford the desired product as a white solid (200 mg). MS (ESI pos. ion) m/z: 319.1. 1H NMR (300 MHz, CDCl3) δ ppm 1.42 (d, J=6.58 Hz, 3H) 2.32-2.47 (m, 2H) 2.49-2.63 (m, 5H) 3.50 (q, J=6.33 Hz, 1H) 3.71 (t, J=4.38 Hz, 4H) 5.49 (br. s., 2H) 8.29 (s, 1H) 8.46 (dd, J=9.13, 2.27 Hz, 1H).

Workup

  1. customThe resulting mixture was degassed
  2. customby bubbling N2 for 5 min
  3. customthen sealed off
  4. customThe reaction mixture was partitioned between 25% IPA in CHCl3 (1% NH4OH) (30 mL) and water (50 mL)
  5. extractionThe aqueous layer was extracted with more 25% IPA in CHCl3 (2×10 mL)
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. concentrationconcentrated
  8. customThe crude product was purified by column chromatography (40 g, 3% MeOH in DCM)

Sources & evidence

ORD record
ord-c8d45597d710416c8114702d7fac9860
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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