Thionyl Chloride → 1-{[1-(2-Aminopyrimidin-4-yl)-6-bromoindazol-3-yl]carbonyl}azetidin-3-ol

HRID 1398580Notes

Reaction equation

HRID 1398580 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([Br:17])[CH:15]=3)[C:10]([C:18]([OH:20])=O)=[N:9]2)[CH:5]=[CH:4][N:3]=1.S(Cl)(Cl)=O.Cl.[NH:26]1[CH2:29][CH:28]([OH:30])[CH2:27]1.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([Br:17])[CH:15]=3)[C:10]([C:18]([N:26]3[CH2:29][CH:28]([OH:30])[CH2:27]3)=[O:20])=[N:9]2)[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 27592903-Hydroxyazetidine hydrochlorideHCID 681819661-(2-Aminopyrimidin-4-yl)-6-bromoindazole-3-carboxylic acid

Product 1

HCID 681817941-{[1-(2-Aminopyrimidin-4-yl)-6-bromoindazol-3-yl]carbonyl}azetidin-3-olYield 49.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 1-(2-aminopyrimidin-4-yl)-6-bromoindazole-3-carboxylic acid (0.38 g, 1.12 mmol)) in DCM (5 mL), was added thionyl chloride (0.49 ml, 6.74 mmol) followed by a drop of DMF. The mixture was stirred at 40° C. overnight. The reaction mixture was concentrated in vacuo and DCM added and the concentration repeated (×2). The acid chloride intermediate was suspended in DCM (10 ml), azetidin-3-ol hydrochloride (491.82 mg, 4.49 mmol) followed by DIPEA (0.86 ml, 4.94 mmol). The reaction was stirred at RT for 0.5 hr and then concentrated in vacuo. The residue was diluted with more DCM and water and the organics extracted (2×20 ml DCM). The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo to give the title intermediate (214 mg, LC-MS purity=63%); LC-MS: m/z=+388.95/390.80 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo and DCM
  2. additionadded
  3. concentrationthe concentration
  4. stirringThe reaction was stirred at RT for 0.5 hr
  5. concentrationconcentrated in vacuo
  6. additionThe residue was diluted with more DCM and water
  7. extractionthe organics extracted (2×20 ml DCM)
  8. dry with materialThe combined organic layers were dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f7178482e88b4e2eaed03f9971c62a18
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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