Acetic Acid → HCID 67003523, compound

HRID 2362723Notes

Reaction equation

HRID 2362723 reaction equation
[Cl:1][C:2]1[C:3]([C:22]2[S:26][C:25]([C:27]3([OH:32])[CH2:31][CH2:30][NH:29][CH2:28]3)=[N:24][CH:23]=2)=[C:4]2[CH:10]=[C:9]([I:11])[N:8]([S:12]([C:15]3[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:5]2=[N:6][CH:7]=1.C=O.[C:35](O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1>[Cl:1][C:2]1[C:3]([C:22]2[S:26][C:25]([C:27]3([OH:32])[CH2:31][CH2:30][N:29]([CH3:35])[CH2:28]3)=[N:24][CH:23]=2)=[C:4]2[CH:10]=[C:9]([I:11])[N:8]([S:12]([C:15]3[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 67003760HCID 67003760, compound

Product 1

HCID 67003523HCID 67003523, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ambient solution of 3-(5-(5-chloro-2-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)pyrrolidin-3-ol (Example 117D) (410 mg, 0.682 mmol) in tetrahydrofuran (10 mL) was added formaldehyde (0.254 mL, 3.41 mmol, 37 wt % in water) and acetic acid (0.195 mL, 3.41 mmol). The reaction was stirred at room temperature for 20 minutes, and sodium triacetoxyborohydride (0.723 g, 3.41 mmol) was added in a single portion. The reaction was stirred at room temperature for 1 hour and was quenched by the addition of water and chloroform. The layers were separated, and the aqueous layer was extracted with additional chloroform (2×). The combined organics were dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purifed by flash column chromatography on silica gel, wluting with a gradient of 0 to 8% methanol (containing 1% v/v ammonium hydroxide) in dichloromethane, to give the title compound. MS APCI(+) m/z 614.9 (M+H)+.

Workup

  1. stirringThe reaction was stirred at room temperature for 1 hour
  2. customwas quenched by the addition of water and chloroform
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with additional chloroform (2×)
  5. dry with materialThe combined organics were dried with anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. additioncontaining 1% v/v ammonium hydroxide) in dichloromethane

Sources & evidence

ORD record
ord-9058bba69074406f9917b7ae0b9b1f40
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

Loading…