Acetic Acid → HCID 87302718, compound

HRID 2098828Notes

Reaction equation

HRID 2098828 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[S:10][C:9]([CH:11]=O)=[CH:8][C:6]=2[N:7]=1.C(O)(=O)C.CC(OC([NH:30][CH:31]1[CH2:34][NH:33][CH2:32]1)=O)(C)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[CH3:49][S:50](Cl)(=[O:52])=[O:51]>ClCCCl.CCN(CC)CC>[Cl:1][C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[S:10][C:9]([CH2:11][N:33]3[CH2:34][CH:31]([NH:30][S:50]([CH3:49])(=[O:52])=[O:51])[CH2:32]3)=[CH:8][C:6]=2[N:7]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 31297Methanesulfonyl chlorideHCID 15194053-Aminoazetidine, 3-BOC protectedHCID 5049666Sodium triacetoxyborohydrideHCID 457899852-Chloro-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde

Product 1

HCID 87302718HCID 87302718, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8471TriethylamineSolvent

Procedure

To 2-chloro-4-morpholinothieno[3,2-c]pyrimidine-6-carbaldehyde 10 from Example 3 (100 mg, 0.35 mmol) in 1,2-dichloroethane (2 mL) was added acetic acid (20 μL, 0.35 mmol), and 3-N-BOC-aminoazetidine (78 mg, 0.5 mmol) then Na(OAc)3BH (90 mg, 0.42 mmol). The reaction stirred overnight at room temperature then was quenched with water and extracted with DCM. The combined organics were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was dissolved in CH2Cl2 (10 mL), MeOH (10 mL), and 4 M HCl in dioxane (10 mL) was added. The resulting mixture stirred at room temperature for 1 h then was concentrated in vacuo. The crude material was dissolved in CH2Cl2 (5 mL) and Et3N (4 mL) and methanesulfonyl chloride (110 μL, 1.4 mmol) was added. The reaction mixture stirred at room temperature overnight then was quenched by the addition of water and extracted with EtOAc. The combined organics were dried over Na2SO4, filtered, and concentrated in vacuo to give N-(1-((2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)azetidin-3-yl)methanesulfonamide which was utilized in a Suzuki coupling according to General Procedure A using 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole 7 to provide 381 after reverse phase HPLC purification (2 mg). MS (Q1) 500 (M)+

Workup

  1. customthen was quenched with water
  2. extractionextracted with DCM
  3. dry with materialThe combined organics were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe crude product was dissolved in CH2Cl2 (10 mL)
  7. additionMeOH (10 mL), and 4 M HCl in dioxane (10 mL) was added
  8. stirringThe resulting mixture stirred at room temperature for 1 h
  9. concentrationthen was concentrated in vacuo
  10. dissolutionThe crude material was dissolved in CH2Cl2 (5 mL)
  11. stirringThe reaction mixture stirred at room temperature overnight
  12. customthen was quenched by the addition of water
  13. extractionextracted with EtOAc
  14. dry with materialThe combined organics were dried over Na2SO4
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ba9457ca9c2d4f2eb1a0c1bbcfbe6e97
Source dataset
uspto-grants-2013_05
Patent number
US08450315B2

Reaction notes

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