Diisopropylethylamine → HCID 69675680, compound

HRID 1616070Notes

Reaction equation

HRID 1616070 reaction equation
[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6](Cl)[N:5]=[CH:4][N:3]=1.[F:11][C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[N:18]=[C:17]([CH:22]([NH2:24])[CH3:23])[C:16]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=1)=[C:15]2[C:31]1[O:35][N:34]=[C:33]([CH3:36])[N:32]=1.CCN(C(C)C)C(C)C>C(O)CCC.C(Cl)Cl.CCCCCC>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([NH:24][CH:22]([C:17]2[C:16]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=3)=[C:15]([C:31]3[O:35][N:34]=[C:33]([CH3:36])[N:32]=3)[C:14]3[C:19](=[CH:20][CH:21]=[C:12]([F:11])[CH:13]=3)[N:18]=2)[CH3:23])[N:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 122782624-Amino-6-chloropyrimidine-5-carbonitrileHCID 69675631HCID 69675631, compound

Product 1

HCID 69675680HCID 69675680, compound

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 21226440Methylenechloride HexaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 4-amino-6-chloropyrimidine-5-carbonitrile (0.068 g, 0.440 mmol), 1-(6-fluoro-4-(3-methyl-1,2,4-oxadiazol-5-yl)-3-(pyridin-2-yl)quinolin-2-yl)-ethanamine (0.1536 g, 0.440 mmol), and n,n-diisopropylethylamine (0.383 mL, 2.198 mmol) in 1-butanol (4.40 mL) was stirred at 120° C. After 14.5 h, the mixture was removed from the heat and to the cooled mixture was added water (50 mL) and DCM (50 mL). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo to give the crude material. The crude material was purified by silica gel column chromatography eluting with a gradient of 0% to 50% DCM:MeOH:NH4OH (89:9:1) in DCM, to provide a tan solid. The tan solid was suspended in DCM-hexane (1:1) and filtered to give 4-amino-6-((1-(6-fluoro-4-(3-methyl-1,2,4-oxadiazol-5-yl)-3-(2-pyridinyl)-2-quinolinyl)ethyl)amino)-5-pyrimidinecarbonitrile as a white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.55-8.62 (1H, m), 8.27 (1H, dd, J=9.2, 5.5 Hz), 7.86-7.93 (2H, m), 7.76-7.85 (2H, m), 7.58 (1H, d, J=7.0 Hz), 7.44-7.51 (1H, m), 7.37 (1H, ddd, J=7.6, 4.9, 1.0 Hz), 7.23 (2H, br. s.), 5.55 (1H, quin, J=6.7 Hz), 2.38 (3H, s), 1.39 (3H, d, J=6.7 Hz); LC-MS (ESI) m/z 468.1 [M+H]+.

Workup

  1. customthe mixture was removed from the
  2. temperatureheat and to the cooled mixture
  3. additionwas added water (50 mL) and DCM (50 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give the crude material
  8. customThe crude material was purified by silica gel column chromatography
  9. washeluting with a gradient of 0% to 50% DCM:MeOH:NH4OH (89:9:1) in DCM
  10. customto provide a tan solid
  11. filtrationfiltered

Sources & evidence

ORD record
ord-e13d471b27b84c5d9ebf31bcf781bef2
Source dataset
uspto-grants-2014_07
Patent number
US08765768B2

Reaction notes

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