Acetic Acid → HCID 67003874, compound

HRID 2362627Notes

Reaction equation

HRID 2362627 reaction equation
[Cl:1][C:2]1[C:3]([C:29]2[S:33][C:32]([C:34]3([OH:38])[CH2:37][CH2:36][CH2:35]3)=[N:31][CH:30]=2)=[C:4]2[CH:10]=[C:9]([C:11]3[CH:18]=[CH:17][C:14]([CH:15]=O)=[CH:13][CH:12]=3)[N:8]([S:19]([C:22]3[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=3)(=[O:21])=[O:20])[C:5]2=[N:6][CH:7]=1.C(O)(=O)C.S([O-])([O-])(=O)=O.[Na+].[Na+].[NH:50]1[CH2:54][CH2:53][CH2:52][CH2:51]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1>[Cl:1][C:2]1[C:3]([C:29]2[S:33][C:32]([C:34]3([OH:38])[CH2:37][CH2:36][CH2:35]3)=[N:31][CH:30]=2)=[C:4]2[CH:10]=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([CH2:15][N:50]4[CH2:54][CH2:53][CH2:52][CH2:51]4)=[CH:17][CH:18]=3)[N:8]([S:19]([C:22]3[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=3)(=[O:21])=[O:20])[C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 24436Sodium SulfateHCID 31268PyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 86659279HCID 86659279, compound

Product 1

HCID 67003874HCID 67003874, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(5-chloro-4-(2-(1-hydroxycyclobutyl)thiazol-5-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-2-yl)benzaldehyde (Example 8B) (2.10 g, 3.72 mmol) in tetrahydrofuran (33.8 mL) was added sequentially acetic acid (0.426 mL, 7.45 mmol), sodium sulfate (1.058 g, 7.45 mmol), and pyrrolidine (0.466 ml, 5.58 mmol). The reaction was stirred for 0.5 hours at ambient temperature, and sodium triacetoxyborohydride (1.578 g, 7.45 mmol) was added in a single portion. The reaction was stirred for 1 hour and was then quenched by the addition of saturated aqueous sodium bicarbonate solution (20 mL), ethyl acetate (20 mL), and solid sodium bicarbonate. The layers were separated, and the aqueous layer was extracted with addition ethyl acetate (2×). The combined organics were dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel, eluting with a gradient of 0 to 10% methanol in dichloromethane with 1% v/v aqueous ammonium hydroxide solution, to give the title compound. MS ESI(+) m/z 619.3 [M+H]+.

Workup

  1. stirringThe reaction was stirred for 1 hour
  2. customwas then quenched by the addition of saturated aqueous sodium bicarbonate solution (20 mL), ethyl acetate (20 mL), and solid sodium bicarbonate
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with addition ethyl acetate (2×)
  5. dry with materialThe combined organics were dried with anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash chromatography on silica gel
  9. washeluting with a gradient of 0 to 10% methanol in dichloromethane with 1% v/v aqueous ammonium hydroxide solution

Sources & evidence

ORD record
ord-f781c82b3b2a414da29b6d114af260af
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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