Hydrochloric Acid → 4-Iodo-2-([1,2]thiazolo[4,5-c]pyridin-7-yl)furo[2,3-c]pyridin-7-amine

HRID 389558Notes

Reaction equation

HRID 389558 reaction equation
C(OC([N:8](C(OC(C)(C)C)=O)[C:9]1[N:10]=[CH:11][CH:12]=[C:13]2[CH:17]=[C:16](B(O)O)[O:15][C:14]=12)=O)(C)(C)C.Br[C:29]1[C:30]2[S:37][N:36]=[CH:35][C:31]=2[CH:32]=[N:33][CH:34]=1.C(=O)([O-])[O-].[K+].[K+].Cl.C1C(=O)N([I:52])C(=O)C1>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CO.O.O1CCOCC1>[I:52][C:12]1[CH:11]=[N:10][C:9]([NH2:8])=[C:14]2[O:15][C:16]([C:29]3[C:30]4[S:37][N:36]=[CH:35][C:31]=4[CH:32]=[N:33][CH:34]=3)=[CH:17][C:13]=12

Participants

11

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 120273N-IodosuccinimideHCID 667600997-Bromo[1,2]thiazolo[4,5-c]pyridineHCID 66761297{7-[Bis(tert-butoxycarbonyl)amino]furo[2,3-c]pyridin-2-yl}boronic acid

Product 1

HCID 667603344-Iodo-2-([1,2]thiazolo[4,5-c]pyridin-7-yl)furo[2,3-c]pyridin-7-amineYield 57.1%

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of {7-[bis(tert-butoxycarbonyl)amino]furo[2,3-c]pyridin-2-yl}boronic acid (82.6 mg, 0.219 mmol), 7-bromo[1,2]thiazolo[4,5-c]pyridine (47.0 mg, 0.218 mmol), Pd(PPh3)4 (12.6 mg, 0.0109 mmol), and potassium carbonate (90.6 mg, 0.656 mmol) in 4:1 1,4-dioxane:water (2 mL) was heated to 70° C. for 30 min. Aqueous 12 N hydrochloric acid (0.3 mL, 3 mmol) and methanol (6 mL) was added at 70° C., and the solution was stirred for 2 h. The organic solvents were removed in vacuo, and the material was extracted with DCM and saturated aqueous sodium bicarbonate. The organic layer was purified by column chromatography (1 to 3% 7 N ammonia/methanol:DCM). The purified intermediate was treated with NIS (15.0 mg, 0.0667 mmol) in DMF (1 mL), and the mixture was heated to 40° C. for 20 min. The material was extracted with EtOAc, and washed with aqueous 1 M sodium thiosulfate and brine (2×). The organic layer was concentrated in vacuo to afford 15 mg (17%) of the title compound as a yellow solid. MS (ESI): 395.39 [M+H]+; HPLC tR=1.06 min (HPLC: polar—2 min).

Workup

  1. customThe organic solvents were removed in vacuo
  2. extractionthe material was extracted with DCM and saturated aqueous sodium bicarbonate
  3. customThe organic layer was purified by column chromatography (1 to 3% 7 N ammonia/methanol:DCM)
  4. extractionThe material was extracted with EtOAc
  5. washwashed with aqueous 1 M sodium thiosulfate and brine (2×)
  6. concentrationThe organic layer was concentrated in vacuo

Sources & evidence

ORD record
ord-6417ab274d0c40d887fa0f719c16d6cf
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

Loading…