Diisopropylethylamine → HCID 178463559, compound

HRID 2036582Notes

Reaction equation

HRID 2036582 reaction equation
Cl[C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[NH:4][CH:5]=[N:6]2.[F:11][C:12]1[CH:13]=[CH:14][C:15]2[N:19]=[C:18]([CH:20]([NH2:22])[CH3:21])[N:17]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=3)[C:16]=2[CH:30]=1.CCN(C(C)C)C(C)C>C(O)CCC>[F:11][C:12]1[CH:13]=[CH:14][C:15]2[N:19]=[C:18]([CH:20]([NH:22][C:2]3[N:10]=[CH:9][N:8]=[C:7]4[C:3]=3[N:4]=[CH:5][NH:6]4)[CH3:21])[N:17]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=3)[C:16]=2[CH:30]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 53592776-ChloropurineHCID 58459122HCID 58459122, compound

Product 1

HCID 178463559HCID 178463559, compound

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
120 °C

Procedure

To a microwave vessel was added 6-chloropurine (0.113 g, 0.732 mmol), 1-(6-fluoro-1-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)ethanamine (Prepared in Example 22, 0.200 g, 0.732 mmol), and DIEA (0.256 mL, 1.46 mmol) in n-butanol (3.66 mL). The solution was stirred at 120° C. for 3 h, filtered and the resulting precipitate was washed with EtOAc:hexane (1:4) to give an off-white solid. The solid was purified by column chromatography on a silica gel column using 10 to 90% gradient of DCM:MeOH:NH4OH (90:10:1) in DCM as eluent to give an off-white solid. This material was triturated in EtOAc:hexane (1:3) and the suspension was filtered to give N-(1-(6-fluoro-1-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)ethyl)-9H-purin-6-amine as an off-white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 1.60 (d, J=6.65 Hz, 3H) 5.57 (br. s., 1H) 6.94 (dd, J=8.90, 2.25 Hz, 1H) 7.11 (td, J=9.39, 2.35 Hz, 1H) 7.29 (t, J=7.04 Hz, 1H) 7.40-7.47 (m, 1H) 7.47-7.63 (m, 2H) 7.70 (dd, J=8.80, 4.89 Hz, 1H) 7.94 (s, 1H) 8.07 (s, 1H) 8.12 (s, 1H) 12.78 (br. s., 1H); LC-MS (ESI) m/z 392.1 [M+H]+.

Workup

  1. filtrationfiltered
  2. washthe resulting precipitate was washed with EtOAc:hexane (1:4)
  3. customto give an off-white solid
  4. customThe solid was purified by column chromatography on a silica gel column
  5. customto give an off-white solid
  6. customThis material was triturated in EtOAc:hexane (1:3)
  7. filtrationthe suspension was filtered

Sources & evidence

ORD record
ord-f68cc16d27d84a099bd5ac413e917576
Source dataset
uspto-grants-2013_11
Patent number
US08575183B2

Reaction notes

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