3,3-Difluoroazetidine hydrochloride → HCID 86676936, compound

HRID 337318Notes

Reaction equation

HRID 337318 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:16]=[CH:15][C:14]([O:17][C:18]([CH3:22])([CH3:21])[CH:19]=O)=[CH:13][CH:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.Cl.[F:24][C:25]1([F:29])[CH2:28][NH:27][CH2:26]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C([O-])(O)=O.[Na+]>[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:12]=[CH:13][C:14]([O:17][C:18]([CH3:21])([CH3:22])[CH2:19][N:27]3[CH2:28][C:25]([F:29])([F:24])[CH2:26]3)=[CH:15][N:16]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1

Participants

6

Reactant 3

HCID 27582473,3-Difluoroazetidine hydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 86662317HCID 86662317, compound

Product 1

HCID 86676936HCID 86676936, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 2-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yloxy)-2-methylpropanal (665 mg, 2.06 mmol, Eq: 1.00) in DCE (70 ml) was added 3,3-difluoroazetidine hydrochloride (347 mg, 2.68 mmol, Eq: 1.30). The mixture was stirred at RT for 1 h, then sodium triacetoxyborohydride (655 mg, 3.09 mmol, Eq: 1.5) was added and stirring was continued for 18 h. The reaction mixture was diluted with saturated NaHCO3 solution and extracted with DCM (5×20 mL). The organic layer was dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by chromatography (SiO2-50 g, Hex:AcOEt, 7:3 in 20 min, then 50% in 30 min) to afford the desired product (566 mg) as a white powder. (M+H)+=400 m/e. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.29 (s, 6 H) 2.79 (br. s., 2 H) 3.70-3.81 (m, 4 H) 3.83 (s, 3 H) 6.87 (dd, J=8.84, 0.51 Hz, 1 H) 7.32 (d, J=8.59 Hz, 1 H) 8.10 (d, J=2.78 Hz, 1 H) 8.22 (s, 1 H) 8.28 (s, 1 H).

Workup

  1. stirringstirring
  2. waitwas continued for 18 h
  3. extractionextracted with DCM (5×20 mL)
  4. dry with materialThe organic layer was dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was purified by chromatography (SiO2-50 g, Hex
  7. waitAcOEt, 7:3 in 20 min

Sources & evidence

ORD record
ord-2b66718296b847b9a893cc773af58317
Source dataset
uspto-grants-2014_11
Patent number
US08889682B2

Reaction notes

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