2-Methoxyethylamine → HCID 118092611, compound

HRID 2207390Notes

Reaction equation

HRID 2207390 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]([NH:15][C:16]3[N:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][N:17]=3)[CH:11]=[C:12]([CH3:14])[CH:13]=2)[CH:5]=[N:6][CH:7]=1.[CH3:26][O:27][CH2:28][CH2:29][NH2:30].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:26][O:27][CH2:28][CH2:29][NH:30][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]([NH:15][C:16]3[N:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][N:17]=3)[CH:11]=[C:12]([CH3:14])[CH:13]=2)[CH:5]=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 80182-MethoxyethylamineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 131735902HCID 131735902, compound

Product 1

HCID 118092611HCID 118092611, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of N-[3-(5-bromopyridin-3-yl)-5-methylphenyl]-4-(trifluoromethyl)pyrimidin-2-amine (35.0 mg, 0.128 mmol), 2-methoxyethanamine (9.61 mg, 0.128 mmol), Pd2(dba)3 (7.83 mg, 0.0086 mmol), Xantphos (14.9 mg, 0.026 mmol), and Cs2CO3 (69.7 mg, 0.214 mmol) in 1,4-dioxane (0.855 mL, 0.1 M) was purged with argon and heated to 90° C. for 12 hours. The reaction mixture was cooled to room temperature and DMSO (1.00 mL) and Si-Thiol (23.4 mg, 1.84 mmol/g) were added to the reaction mixture. The reaction mixture was stir at room temperature for 4 hours and then passed through a filter, concentrated in vacuo, and the crude residue was purified by reverse phase preparative HPLC (0:100 to 95:5 acetonitrile:water: 0.1% v/v formic acid modifier) to afford N-(3-{5-[(2-methoxyethyl)amino]pyridin-3-yl}-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine as the formic acid salt. MS APCI calc'd for C20H21F3N4O [M+H]+ 404. found 404. 1H NMR (600 MHz, DMSO-d6) δ 10.20 (s, 1H), 8.80 (d, J=4.9 Hz, 1H), 7.97 (d, J=5.6 Hz, 2H), 7.87 (s, 1H), 7.50 (s, 1H), 7.24 (d, J=4.9 Hz, 1H), 7.09 (d, J=6.1 Hz, 2H), 3.49 (t, J=5.5 Hz, 2H), 3.33-3.22 (m, 5H), 2.32 (s, 3H).

Workup

  1. customwas purged with argon
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additionDMSO (1.00 mL) and Si-Thiol (23.4 mg, 1.84 mmol/g) were added to the reaction mixture
  4. concentrationconcentrated in vacuo
  5. customthe crude residue was purified by reverse phase preparative HPLC (0:100 to 95:5 acetonitrile:water: 0.1% v/v formic acid modifier)

Sources & evidence

ORD record
ord-9894ccde978544f0bfc13f9976bc13e9
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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