Morpholine → 3-morpholino-7-(pyridin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amine

HRID 335933Notes

Reaction equation

HRID 335933 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:15]3([CH2:19][S:18][C:17]([N:20]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])=[N:16]3)[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:37]4[CH:38]=[N:39][CH:40]=[CH:41][CH:42]=4)[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1.CC(C)([O-])C.[Na+].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.[NH:91]1[CH2:96][CH2:95][O:94][CH2:93][CH2:92]1>CCOC(C)=O.C([O-])(=O)C.C([O-])(=O)C.[Pd+2].O1CCOCC1>[O:94]1[CH2:95][CH2:96][N:91]([C:2]2[CH:3]=[C:4]3[C:15]4([CH2:19][S:18][C:17]([N:20]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])=[N:16]4)[C:14]4[C:9](=[CH:10][CH:11]=[C:12]([C:37]5[CH:38]=[N:39][CH:40]=[CH:41][CH:42]=5)[CH:13]=4)[O:8][C:5]3=[N:6][CH:7]=2)[CH2:92][CH2:93]1

Participants

8

Reactant 4

HCID 8083MorpholineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 673833213-bromo-7-(pyridin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amine

Product 1

HCID 674368683-morpholino-7-(pyridin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amine

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A vial was charged with 3-bromo-7-(pyridin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine (0.080 g, 0.117 mmol), palladium diacetate (2.62 mg, 0.012 mmol), sodium tert-butoxide (0.071 ml, 0.583 mmol), and xantphos (0.013 g, 0.023 mmol). Dioxane (1.166 ml) and morpholine (0.030 ml, 0.350 mmol) were added sequentially and the reaction was stirred at 100° C. for 24 hours. The mixture was cooled to RT and was diluted with EtOAc (20 mL) and washed with water. The aqueous layer was extracted with EtOAc (3×15 mL), and the combined organic layers were, dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (RediSep 12 g, gradient elution 0-100% EtOAc:Hex) to afford 3-morpholino-7-(pyridin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine as an off-white solid.

Workup

  1. temperatureThe mixture was cooled to RT
  2. washwashed with water
  3. extractionThe aqueous layer was extracted with EtOAc (3×15 mL)
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe material was purified via column chromatography (RediSep 12 g, gradient elution 0-100% EtOAc:Hex)

Sources & evidence

ORD record
ord-0a17d3ec5c8b4e3eb8f6c25610ea67ad
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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