Water → 4-amino-6-(1-(7-bromo-1-(5-fluoropyridin-3-yl)-1H-benzo[d]imidazol-2-yl)ethylamino)pyrimidine-5-carbonitrile

HRID 2036668Notes

Reaction equation

HRID 2036668 reaction equation
[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6](Cl)[N:5]=[CH:4][N:3]=1.[Br:11][C:12]1[C:17]2[N:18]([C:24]3[CH:25]=[N:26][CH:27]=[C:28]([F:30])[CH:29]=3)[C:19]([CH:21]([NH2:23])[CH3:22])=[N:20][C:16]=2[CH:15]=[CH:14][CH:13]=1.CCN(C(C)C)C(C)C.O>C(O)CCC.CCOC(C)=O.CCCCCC>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([NH:23][CH:21]([C:19]2[N:18]([C:24]3[CH:25]=[N:26][CH:27]=[C:28]([F:30])[CH:29]=3)[C:17]3[C:12]([Br:11])=[CH:13][CH:14]=[CH:15][C:16]=3[N:20]=2)[CH3:22])[N:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 122782624-Amino-6-chloropyrimidine-5-carbonitrileHCID 584593161-(7-bromo-1-(5-fluoropyridin-3-yl)-1H-benzo[d]imidazol-2-yl)ethanamine

Product 1

HCID 534821944-amino-6-(1-(7-bromo-1-(5-fluoropyridin-3-yl)-1H-benzo[d]imidazol-2-yl)ethylamino)pyrimidine-5-carbonitrile

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 4-amino-6-chloropyrimidine-5-carbonitrile (0.368 g, 2.381 mmol), 1-(7-bromo-1-(5-fluoropyridin-3-yl)-1H-benzo[d]imidazol-2-yl)ethanamine (0.798 g, 2.38 mmol), and DIEA (1.24 mL, 7.14 mmol) in 1-butanol (23.8 mL) was stirred at 120° C. After 23 h, the mixture was removed from the heat and left at rt. After cooling, the mixture was concentrated in vacuo to give a dark purple solid. To the dark purple solid was added water (50 mL) followed by sonication. The resulting precipitate was collected by filtration, washed with water, and air-dried to give the product. The solid was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep™ pre-packed silica gel column (80 g), eluting with a gradient of 0% to 50% DCM:MeOH:NH4OH (89:9:1) in DCM, to provide a purple solid. The purple solid was suspended in EtOAc-hexane (1:5, 10 mL), filtered, and washed with EtOAc-hexane (1:5, 40 mL) to provide 4-amino-6-(1-(7-bromo-1-(5-fluoropyridin-3-yl)-1H-benzo[d]imidazol-2-yl)ethylamino)pyrimidine-5-carbonitrile as a purple solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.47-8.79 (2H, m), 7.88-8.34 (1H, m), 7.67-7.85 (3H, m), 7.44 (1H, dd, J=7.8, 0.8 Hz), 7.22 (3H, t, J=7.9 Hz), 5.29-5.47 (1H, m), 1.57 (3H, d, J=6.8 Hz); LC-MS (ESI) m/z 453.0 [M+H (79Br)]+ and 454.9 [M+H (81Br)]+.

Workup

  1. customthe mixture was removed from the
  2. temperatureheat
  3. waitleft at rt
  4. temperatureAfter cooling
  5. concentrationthe mixture was concentrated in vacuo
  6. customto give a dark purple solid
  7. customfollowed by sonication
  8. filtrationThe resulting precipitate was collected by filtration
  9. washwashed with water
  10. customair-dried
  11. customto give the product
  12. customThe solid was absorbed onto a plug of silica gel
  13. custompurified by chromatography through a Redi-Sep™ pre-packed silica gel column (80 g)
  14. washeluting with a gradient of 0% to 50% DCM:MeOH:NH4OH (89:9:1) in DCM
  15. customto provide a purple solid
  16. filtrationfiltered
  17. washwashed with EtOAc-hexane (1:5, 40 mL)

Sources & evidence

ORD record
ord-a12937a63238459c8231d6a8dbdef362
Source dataset
uspto-grants-2013_11
Patent number
US08575183B2

Reaction notes

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