Trifluoroacetic acid → 3-morpholino-7-(pyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amine

HRID 335934Notes

Reaction equation

HRID 335934 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:8]=[C:9]3[C:20]4([CH2:24][S:23][C:22]([N:25](COCC[Si](C)(C)C)COCC[Si](C)(C)C)=[N:21]4)[C:19]4[C:14](=[CH:15][CH:16]=[C:17]([C:42]5[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=5)[CH:18]=4)[O:13][C:10]3=[N:11][CH:12]=2)[CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[O:1]1[CH2:2][CH2:3][N:4]([C:7]2[CH:8]=[C:9]3[C:20]4([CH2:24][S:23][C:22]([NH2:25])=[N:21]4)[C:19]4[C:14](=[CH:15][CH:16]=[C:17]([C:42]5[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=5)[CH:18]=4)[O:13][C:10]3=[N:11][CH:12]=2)[CH2:5][CH2:6]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 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

Product 1

HCID 584662923-morpholino-7-(pyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
50 °C

Procedure

A solution of 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 (0.066 g, 0.095 mmol) in 5 mL of DCM was treated with TFA (0.5 ml, 6.49 mmol). The reaction was stirred for 3 hrs at 50° C. The mixture was cooled to RT and was diluted with DCM (25 mL). The derived solution was washed with saturated sodium bicarbonate (50 mL). The aqueous layer was extracted with DCM (3×15 mL) and the combined organic layers were washed with brine, dried with sodium sulfate, filtered, and concentrated. The material was purified by column chromatography (RediSep 12 g, gradient elution 0-100% DCM: 100:10:1 DCM, MeOH, NH4OH) to provide 3-morpholino-7-(pyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine as a racemic mixture. Chiral separation provided (S)-3-morpholino-7-(pyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine and (R)-3-morpholino-7-(pyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine, both isomers as a white solid. MS m/z=432.3.

Workup

  1. temperatureThe mixture was cooled to RT
  2. washThe derived solution was washed with saturated sodium bicarbonate (50 mL)
  3. extractionThe aqueous layer was extracted with DCM (3×15 mL)
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe material was purified by column chromatography (RediSep 12 g, gradient elution 0-100% DCM: 100:10:1 DCM, MeOH, NH4OH)

Sources & evidence

ORD record
ord-ea8dd8c9eb604abc91daff745684cb91
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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