Ammonium Hydroxide → Tert-butyl ((6-bromothiazolo[5,4-b]pyridin-2-yl)methyl)carbamate

HRID 1487535Notes

Reaction equation

HRID 1487535 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([CH2:11]Br)[S:8][C:5]2=[N:6][CH:7]=1.[OH-].[NH4+:14].[CH3:15][C:16]([O:19][C:20]([O:22]C(OC(C)(C)C)=O)=O)([CH3:18])[CH3:17]>O1CCCC1.C([O-])(O)=O.[Na+]>[Br:1][C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([CH2:11][NH:14][C:20](=[O:22])[O:19][C:16]([CH3:18])([CH3:17])[CH3:15])[S:8][C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 14923Ammonium HydroxideHCID 90495Di-tert-butyl dicarbonateHCID 594027536-Bromo-2-(bromomethyl)thiazolo[5,4-b]pyridine

Product 1

HCID 86695489Tert-butyl ((6-bromothiazolo[5,4-b]pyridin-2-yl)methyl)carbamate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

To a solution 6-bromo-2-(bromomethyl)thiazolo[5,4-b]pyridine (800 mg, 2.60 mmol) (Journal of Medicinal Chemistry, 53(10), 3927-3936; 2010) in tetrahydrofuran (10 mL) is added ammonium hydroxide (2 mL) and stirred at room temperature for 16 hours. Reaction is concentrated, diluted with water (5 mL) and extracted using ethyl acetate (3×10 ml). Extracts are dried over Na2SO4 and concentrated to get crude product (650 mg). m/z (CI) M+244. To a solution of crude amine (350 mg, 1.43 mmol) in tetrahydrofuran (10 mL) and aqueous NaHCO3 (2 mL) is added boc anhydride and resulting mixture stirred at room temperature for over night. Organic solution is separated and aqueous layer extracted with ethyl acetate (5 mL). Combined organic solution is dried over Na2SO4 and concentrated under vacuum to give the title compound (400 mg): 1H NMR (400 MHz, CDCl3) 1.50 (s, 9H), 4.74 (d, 2H), 8.36 (s, 1H), 8.62 (s, 1H). m/z (CI) M+2 346.

Workup

  1. customReaction
  2. concentrationis concentrated
  3. additiondiluted with water (5 mL)
  4. extractionextracted
  5. dry with materialExtracts are dried over Na2SO4
  6. concentrationconcentrated
  7. customto get crude product (650 mg)
  8. customresulting mixture
  9. stirringstirred at room temperature for over night
  10. customOrganic solution is separated
  11. extractionaqueous layer extracted with ethyl acetate (5 mL)
  12. dry with materialCombined organic solution is dried over Na2SO4
  13. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-7c99ab48b4c24de29f84a01d692dd803
Source dataset
uspto-grants-2016_08
Patent number
US09428528B2

Reaction notes

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