Water → 1,1-dimethylethyl 5-(4-amino-7-iodofuro[3,2-c]pyridin-3-yl)-2,3-dihydro-1H-indole-1-carboxylate

HRID 1910076Notes

Reaction equation

HRID 1910076 reaction equation
C1C(=O)N([I:8])C(=O)C1.[NH2:9][C:10]1[C:15]2[C:16]([C:19]3[CH:20]=[C:21]4[C:25](=[CH:26][CH:27]=3)[N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:23][CH2:22]4)=[CH:17][O:18][C:14]=2[CH:13]=[CH:12][N:11]=1.O>CN(C=O)C>[NH2:9][C:10]1[C:15]2[C:16]([C:19]3[CH:20]=[C:21]4[C:25](=[CH:26][CH:27]=3)[N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:23][CH2:22]4)=[CH:17][O:18][C:14]=2[C:13]([I:8])=[CH:12][N:11]=1

Participants

5

Reactant 3

HCID 962WaterHCID 120273N-Iodosuccinimide2×HCID 668240741,1-dimethylethyl 5-(4-aminofuro[3,2-c]pyridin-3-yl)-2,3-dihydro-1H-indole-1-carboxylate

Product 1

HCID 668237261,1-dimethylethyl 5-(4-amino-7-iodofuro[3,2-c]pyridin-3-yl)-2,3-dihydro-1H-indole-1-carboxylateYield 93.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A solution of NIS (0.985 g, 4.38 mmol) in DMF (20 mL) was added dropwise to a solution of 1,1-dimethylethyl 5-(4-aminofuro[3,2-c]pyridin-3-yl)-2,3-dihydro-1H-indole-1-carboxylate (1.505 g, 4.28 mmol) in DMF (20 mL) at −40° C. under Nitrogen. The mixture was stirred and allowed to slowly warm to room temperature for 17 hours. LCMS indicated about 85% conversion, so the mixture was cooled to about −30° C. and another portion of NIS (0.193 g, 0.858 mmol) in DMF (3 mL) was added dropwise. It was then allowed to slowly warm to room temperature and stirred for another 24 hours. The reaction mixture was then poured into water (ca. 200 mL) and the precipitate was collected by vacuum filtration and rinsed with Et2O (50 mL) to give 1,1-dimethylethyl 5-(4-amino-7-iodofuro[3,2-c]pyridin-3-yl)-2,3-dihydro-1H-indole-1-carboxylate (2.384 g, 4.00 mmol, 93% yield) as a tan solid. LC/MS (ES) m/z=478 [M+H]+.

Workup

  1. temperatureso the mixture was cooled to about −30° C.
  2. temperatureto slowly warm to room temperature
  3. stirringstirred for another 24 hours
  4. filtrationthe precipitate was collected by vacuum filtration
  5. washrinsed with Et2O (50 mL)

Sources & evidence

ORD record
ord-fe7bf380f06f4d21a6a879c3befecd15
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

Loading…