Acetic Acid → HCID 67003710, compound

HRID 2362703Notes

Reaction equation

HRID 2362703 reaction equation
[F:1][C:2]1[C:3]([C:21]2[S:25][C:24]([C:26]3([OH:30])[CH2:29][NH:28][CH2:27]3)=[N:23][CH:22]=2)=[C:4]2[CH:10]=[CH:9][N:8]([S:11]([C:14]3[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:5]2=[N:6][CH:7]=1.C=O.Cl[CH:34](Cl)C.C(O)(=O)C.C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>>[F:1][C:2]1[C:3]([C:21]2[S:25][C:24]([C:26]3([OH:30])[CH2:29][N:28]([CH3:34])[CH2:27]3)=[N:23][CH:22]=2)=[C:4]2[CH:10]=[CH:9][N:8]([S:11]([C:14]3[CH:15]=[CH:16][C:17]([CH3:18])=[CH:19][CH:20]=3)(=[O:13])=[O:12])[C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 6

HCID 176Acetic AcidHCID 712FormaldehydeHCID 63651,1-DichloroethaneHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 67003539HCID 67003539, compound

Product 1

HCID 67003710HCID 67003710, compound

Conditions

Temperature
90 °C

Procedure

A round-bottomed flask equipped with a reflux condenser was charged with 3-(5-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)azetidin-3-ol (100 mg, 0.225 mmol) (Example 103A), paraformaldehyde (33.8 mg, 1.125 mmol), dichloroethane (2.5 mL), and acetic acid (0.064 mL, 1.125 mmol). Sodium cyanoborohydride (0.059 ml, 1.125 mmol) was added in three portions, and the mixture heated to 90° C. for 1 hour. The reaction mixture was slowly cooled to room temperature, and then to 0° C. in an ice-bath. Saturated sodium bicarbonate solution was added, and the mixture stirred vigorously for about an hour. The layers were separated, and the aqueous layer was extracted with dichloromethane (3×10 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated to give the title compound. MS APCI(+) m/z 459.24 (M+H)+.

Workup

  1. customA round-bottomed flask equipped with a reflux condenser
  2. temperatureThe reaction mixture was slowly cooled to room temperature
  3. customto 0° C.
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with dichloromethane (3×10 mL)
  6. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-7a26c3e6b10e4973becfdd40aafc876e
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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