Benzeneethanamine, alpha-methyl-, phosphate (1:1) → (S)-7-(2-fluoropyridin-3-yl)-3-(pyrimidin-2-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amine

HRID 335992

Reaction equation

HRID 335992 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C@:15]3([CH2:19][S:18][C:17]([NH2:20])=[N:16]3)[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:21]4[C:22]([F:27])=[N:23][CH:24]=[CH:25][CH:26]=4)[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1.CC(N)CC1C=CC=CC=1.OP(O)(O)=O.C([Sn](CCCC)(CCCC)[C:48]1[N:53]=[CH:52][CH:51]=[CH:50][N:49]=1)CCC>O1CCOCC1>[F:27][C:22]1[C:21]([C:12]2[CH:13]=[C:14]3[C@@:15]4([CH2:19][S:18][C:17]([NH2:20])=[N:16]4)[C:4]4[C:5](=[N:6][CH:7]=[C:2]([C:48]5[N:53]=[CH:52][CH:51]=[CH:50][N:49]=5)[CH:3]=4)[O:8][C:9]3=[CH:10][CH:11]=2)=[CH:26][CH:25]=[CH:24][N:23]=1

Participants

5

Reactant 3

HCID 62885Benzeneethanamine, alpha-methyl-, phosphate (1:1)HCID 27632512-(Tributylstannyl)pyrimidineHCID 67438436(S)-3-bromo-7-(2-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amine

Product 1

HCID 58466117(S)-7-(2-fluoropyridin-3-yl)-3-(pyrimidin-2-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amineYield 12%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A vial was charged with (S)-3-bromo-7-(2-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine (100 mg, 0.23 mmol), AmPhos (15.97 mg, 0.023 mmol), 2-(tributylstannyl)pyrimidine (333 mg, 0.90 mmol) and dioxane (1.50 mL). The vial was purged with Ar (g), sealed, and heated to 100° C. overnight. After cooling to rt, crude was diluted with MeOH (3 mL) and purified with reverse phase HPLC. Fractions containing product were washed with saturated aq. NaHCO3 (15 mL) and extracted with ethyl acetate (1×100 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to provide a white solid, (S)-7-(2-fluoropyridin-3-yl)-3-(pyrimidin-2-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine (12 mg, 0.027 mmol, 12% yield). MS m/z=443.0 [M+H]+. Calc'd for C23H15FN6OS: 442.47.

Workup

  1. customThe vial was purged with Ar (g)
  2. customsealed
  3. temperatureAfter cooling to rt
  4. additioncrude was diluted with MeOH (3 mL)
  5. custompurified with reverse phase HPLC
  6. additionFractions containing product
  7. washwere washed with saturated aq. NaHCO3 (15 mL)
  8. extractionextracted with ethyl acetate (1×100 mL)
  9. dry with materialThe combined organic layers were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-70fd3fccf6804686aae1e94a19690e67
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Linked notes

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