Dimethylformamide → HCID 58860800, compound

HRID 729719Notes

Reaction equation

HRID 729719 reaction equation
[Li]CCCC.Br[C:7]1[CH:12]=[CH:11][C:10](/[C:13](=[CH:22]\[CH:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)/[C:14]([NH:16][C:17]2[S:18][CH:19]=[CH:20][N:21]=2)=[O:15])=[CH:9][CH:8]=1.CN([CH:32]=[O:33])C.S(=O)(O)[O-]>C1COCC1.CCOC(C)=O>[CH:32]([C:19]1[S:18][C:17]([NH:16][C:14](=[O:15])/[C:13](/[C:10]2[CH:11]=[CH:12][CH:7]=[CH:8][CH:9]=2)=[CH:22]/[CH:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)=[N:21][CH:20]=1)=[O:33]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 104748BisulfiteHCID 10069129HCID 10069129, compoundHCID 178418339Butyllithium

Product 1

HCID 58860800HCID 58860800, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

n-BuLi (17 mL of a 1.6M solution in hexanes, 27.2 mmol) was added to a stirred solution of (E)-2-(4-bromophenyl)-3-(tetrahydropyran-4-yl)-N-thiazol-2-ylacrylamide (EXAMPLE 12, 4.00 g, 10.2 mmol) in anhydrous THF (100 mL) at −78° C. After 110 min, the mixture was treated with anhydrous DMF (5 mL, 64.6 mmol), before being allowed to warm to 20° C. over 30 min. The reaction was quenched with 1M HCl, then the THF was evaporated off under reduced pressure. The aqueous phase was extracted with CH2Cl2, then the CH2Cl2 extracts were dried (MgSO4), filtered, and concentrated. The residue was stirred with Na2S2O5 solution. The solid produced was collected and triturated with EtOAc. This material was then suspended in EtOAc, then saturated aqueous NaHCO3 was added with stirring. The layers were separated, then the aqueous phase was extracted with EtOAc and CH2Cl2. The combined organic layers were dried, filtered, concentrated, and subjected to column chromatography (CH2Cl2-THF, 93:7), to give EXAMPLE 125 (RTB=1.30 min; m/z (ES+)=371.2 [M+H]+) and EXAMPLE 126 (RTB=1.38 min; m/z (ES+)=343.4 [M+H]+). The EtOAc washings from the bisulfite addition complex were concentrated, then the residue was subjected to flash chromatography (CH2Cl2-THF, 24:1 to 93:7) to give EXAMPLE 124 (RTB=1.39 min; m/z (ES+)=315.3 [M+H]+) and an additional quantity of EXAMPLE 126.

Workup

  1. customThe reaction was quenched with 1M HCl
  2. customthe THF was evaporated off under reduced pressure
  3. extractionThe aqueous phase was extracted with CH2Cl2
  4. dry with materialthe CH2Cl2 extracts were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe solid produced
  8. customwas collected
  9. customtriturated with EtOAc
  10. additionsaturated aqueous NaHCO3 was added
  11. stirringwith stirring
  12. customThe layers were separated
  13. extractionthe aqueous phase was extracted with EtOAc and CH2Cl2
  14. customThe combined organic layers were dried
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customto give EXAMPLE 125 (RTB=1.30 min; m/z (ES+)=371.2 [M+H]+) and EXAMPLE 126 (RTB=1.38 min; m/z (ES+)=343.4 [M+H]+)
  18. concentrationwere concentrated
  19. customto give EXAMPLE 124 (RTB=1.39 min; m/z (ES+)=315.3 [M+H]+)

Sources & evidence

ORD record
ord-78fcb31b4fb84ea9a30d1fb8aa49998b
Source dataset
uspto-grants-2009_09
Patent number
US07582632B2

Reaction notes

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