4,6-Dichloro-1,3,5-trazin-2-amine → 6-chloro-N-[(S)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethyl]-[1,3,5]triazine-2,4-diamine

HRID 243396Notes

Reaction equation

HRID 243396 reaction equation
Cl.Cl.[F:3][C:4]1[CH:5]=[CH:6][C:7]2[N:11]=[C:10]([C@@H:12]([NH2:14])[CH3:13])[N:9]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:8]=2[CH:21]=1.[Cl:22][C:23]1[N:28]=[C:27](Cl)[N:26]=[C:25]([NH2:30])[N:24]=1.CCN(C(C)C)C(C)C>CC(O)C>[Cl:22][C:23]1[N:28]=[C:27]([NH:14][C@H:12]([C:10]2[N:9]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:8]3[CH:21]=[C:4]([F:3])[CH:5]=[CH:6][C:7]=3[N:11]=2)[CH3:13])[N:26]=[C:25]([NH2:30])[N:24]=1

Participants

5

Reactant 3

HCID 136154,6-Dichloro-1,3,5-trazin-2-amineHCID 81531DiisopropylethylamineHCID 68157580(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride

Product 1

HCID 866688846-chloro-N-[(S)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethyl]-[1,3,5]triazine-2,4-diamine

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To an ice-cooled mixture of (5)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (226 mg, 0.69 mmol), 4,6-dichloro-[1,3,5]triazin-2-ylamine (125 mg, 0.76 mmol) and IPA (5 mL) was added DIPEA (0.59 mL, 3.45 mmol). The reaction mixture was stirred at RT (room temperature) for 64 h. The solvent was removed under reduced pressure and the resulting residue was partitioned between EtOAc and aqueous Na2CO3. The aqueous phase was extracted with EtOAc and the combined organic fractions washed with water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, eluant EtOAc) affording the title compound as a colourless foam (quantitative). A portion (50 mg) was further purified by column chromatography (Si—PCC, eluant EtOAc) affording 269 after evaporation from acetone as a colourless foam (31.8 mg). LCMS (Method K): RT 4.06 min [M+H]+ 384.0/385.9. 1H NMR (DMSO-d6, 400 MHz, 80° C.): δ 7.69 (1H, bs), 7.66 (1H, dd, J=8.8, 4.9 Hz), 7.60-7.50 (5H, m), 7.07-7.02 (1H, m), 6.78 (2H, bs), 6.77 (1H, dd, J=8.9, 2.4 Hz), 5.21 (1H, quintet, J=7.1 Hz), 1.46 (3H, d, J=6.9 Hz)

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe resulting residue was partitioned between EtOAc and aqueous Na2CO3
  3. extractionThe aqueous phase was extracted with EtOAc
  4. washthe combined organic fractions washed with water
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography (Si—PCC, eluant EtOAc)

Sources & evidence

ORD record
ord-7badd8d1f7de40baa72391117a1c4336
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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