2-Methyl-1-butanethiol → HCID 58466179, compound

HRID 335849Notes

Reaction equation

HRID 335849 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C@:15]3([CH2:19][O:18][C:17]([NH2:20])=[N:16]3)[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:21]4[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=4)[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1.[CH3:27][CH:28]([CH2:31][CH3:32])[CH2:29][SH:30].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[CH3:27][CH:28]([CH2:31][CH3:32])[CH2:29][S:30][C:2]1[CH:3]=[C:4]2[C@:15]3([CH2:19][O:18][C:17]([NH2:20])=[N:16]3)[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:21]4[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=4)[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 158772-Methyl-1-butanethiolHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 67241561(5S)-3-bromo-7-(3-pyridinyl)spiro[chromeno[2,3-b]pyridine-5,4'-[1,3]oxazol]-2'-amine

Product 1

HCID 58466179HCID 58466179, compound

Reagents, catalysts & solvents 2

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

Procedure

A mixture of (S)-3-bromo-7-(pyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (53 mg, 0.130 mmol), 2-methylbutane-1-thiol (14.21 mg, 0.130 mmol), tris(dibenzylideneacetone)dipalladium (5.93 mg, 6.48 μmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (3.75 mg, 6.48 μmol), N,N-diethyl-N-isopropylpropan-2-amine (45.1 μL, 0.259 mmol), and dry 1,4-dioxane (0.5 mL) was irradiated in microwave glass vessel at 160° C. for 35 minutes. The whole was cooled to rt and the resulting solid was filtered off and washed with MeOH (3 mL). The filtrates were combined, concentrated, and purified with reverse phase HPLC. Fractions containing the product were combined, and concentrated. TFA was removed using catch and release with strong cation exchange with 2 g SCX columns. First, the material was loaded in the column with MeOH. The column washed with MeOH to remove the TFA, then with 2M NH3 in MeOH to collect the product. The basic wash was collected and dried to afford (4′S)-3-(2-methylbutylthio)-7-(pyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine as a white solid.

Workup

  1. customwas irradiated in microwave glass vessel at 160° C. for 35 minutes
  2. filtrationthe resulting solid was filtered off
  3. washwashed with MeOH (3 mL)
  4. concentrationconcentrated
  5. custompurified with reverse phase HPLC
  6. additionFractions containing the product
  7. concentrationconcentrated
  8. customTFA was removed
  9. washThe column washed with MeOH
  10. customto remove the TFA
  11. customwith 2M NH3 in MeOH to collect the product
  12. washThe basic wash
  13. customwas collected
  14. customdried

Sources & evidence

ORD record
ord-a739224e77d8417bb82e8924908f1bdc
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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