2,6-Dimethylmorpholine, cis- → HCID 71280529, compound

HRID 1497933Notes

Reaction equation

HRID 1497933 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([NH:13][C:14]3[CH:19]=[C:18]([C:20]4[N:24]=[C:23]([CH:25]5[CH2:28][C:27]([F:30])([F:29])[CH2:26]5)[O:22][N:21]=4)[CH:17]=[CH:16][C:15]=3[CH3:31])=[O:12])=[CH:9][N:10]=2)[CH:7]=1.[CH3:32][C@H:33]1[O:38][C@@H:37]([CH3:39])[CH2:36][NH:35][CH2:34]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.CC(C)([O-])C.[Na+]>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]>[F:29][C:27]1([F:30])[CH2:28][CH:25]([C:23]2[O:22][N:21]=[C:20]([C:18]3[CH:17]=[CH:16][C:15]([CH3:31])=[C:14]([NH:13][C:11]([C:8]4[N:6]5[CH:7]=[C:2]([N:35]6[CH2:34][C@@H:33]([CH3:32])[O:38][C@@H:37]([CH3:39])[CH2:36]6)[CH:3]=[CH:4][C:5]5=[N:10][CH:9]=4)=[O:12])[CH:19]=3)[N:24]=2)[CH2:26]1

Participants

7

Reactant 4

HCID 6415002,6-Dimethylmorpholine, cis-HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 71280232HCID 71280232, compound

Product 1

HCID 71280529HCID 71280529, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
125 °C

Procedure

A mixture of 6-bromo-N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (42h) (25 mg, 0.051 mmol), cis-2,6-dimethylmorpholine (9 mg, 0.077 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (4 mg, 0.01 mmol), tris(dibenzylideneacetone)dipalladium(0) (2 mg, 0.003 mmol), and sodium t-butoxide (10 mg, 0.102 mmol) in anhydrous dioxane (1 mL) was heated in the microwave at 125° C. for 25 minutes. The reaction was cooled to room temperature and filtered through a plug of celite. The solvent was concentrated and the crude product was purified by reverse phase preparative HPLC to afford N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-((2S,6R)-2,6-dimethylmorpholino)imidazo[1,2-a]pyridine-3-carboxamide (F96). 1H NMR (400 MHz, d6-DMSO) δ 10.17 (s, 1H), 8.95 (d, J=1.6 Hz, 1H), 8.64 (s, 1H), 8.03 (d, J=1.6 Hz, 1H), 7.84 (dd, J=1.6, 8.0 Hz, 1H), 7.79-7.71 (m, 2H), 7.50 (d, J=8.0 Hz, 1H), 3.91-3.86 (m, 1H), 3.76-3.71 (m, 2H), 3.54-3.51 (m, 2H), 3.23-3.03 (m, 4H), 2.36 (s, 3H), 2.31-2.25 (m, 2H), 1.17 (s, 3H), 1.15 (s, 3H). MS m/z 522.22 (M+1)+.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. filtrationfiltered through a plug of celite
  3. concentrationThe solvent was concentrated
  4. customthe crude product was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-6b9b4f0655b24631869cc1400db36161
Source dataset
uspto-grants-2015_12
Patent number
US09199981B2

Reaction notes

Loading…