Dimethyl Sulfoxide → 6-Chloro-4-(isopropylamino)nicotinaldehyde

HRID 877590Notes

Reaction equation

HRID 877590 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[Cl:11][C:12]1[N:17]=[CH:16][C:15]([CH2:18][OH:19])=[C:14]([NH:20][CH:21]([CH3:23])[CH3:22])[CH:13]=1.CCN(CC)CC>C(Cl)Cl>[Cl:11][C:12]1[CH:13]=[C:14]([NH:20][CH:21]([CH3:23])[CH3:22])[C:15]([CH:18]=[O:19])=[CH:16][N:17]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 89689798(6-Chloro-4-(isopropylamino)pyridin-3-yl)methanol

Product 1

HCID 866201696-Chloro-4-(isopropylamino)nicotinaldehyde

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

To a stirred solution of DMSO (13.43 mmol, 3.5 equiv.) in dry DCM (30 mL), oxalyl chloride (11.51 mmol, 3 equiv.) was added at −78° C. After being stirred for 20 min, (6-chloro-4-(isopropylamino)pyridin-3-yl)methanol (75) (770 mg, 3.84 mmol) was added to the above reaction mixture at −78° C. and stirred for 2 h. The reaction mixture was allowed to warm up to −20° C. and added Et3N (19.19 mmol, 5 equiv.) dropwise over a period of 5 mins. The reaction mixture was allowed to warm up to 0° C. over 30 mins and quenched with ice-flakes followed by 10% NaHCO3 solution. The organic layer was separated, aqueous layer was extracted with DCM (twice). The organic layers were collected together, dried over Na2SO4, filtered and concentrated to give crude aldehyde. The crude material obtained was purified by column chromatography through silica gel and EtOAc: pet ether as eluent provided the desired compound, 6-chloro-4-(isopropylamino)nicotinaldehyde. LC/MS: Acquity BEH C18 2.1×50 mm, 1.8 micron; Solvent A=0.1% TFA in water; Solvent B=0.1% TFA in ACN; gradient 0-100% B over 2 min; retention time: 0.76 min; LCMS (ES-API), m/z 199.26 (M+H).

Workup

  1. stirringstirred for 2 h
  2. temperatureto warm up to 0° C. over 30 mins
  3. customquenched with ice-flakes
  4. customThe organic layer was separated
  5. extractionaqueous layer was extracted with DCM (twice)
  6. customThe organic layers were collected together
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give crude aldehyde
  11. customThe crude material obtained
  12. customwas purified by column chromatography through silica gel and EtOAc

Sources & evidence

ORD record
ord-9debeeeaa6fb4dee878488280f0f871b
Source dataset
uspto-grants-2015_03
Patent number
US08987311B2

Reaction notes

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