Sodium Iodide → HCID 58529569, compound

HRID 1972794Notes

Reaction equation

HRID 1972794 reaction equation
[CH2:1]([N:8]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17]3[CH:18]=[C:19]([CH2:27][CH2:28][CH2:29]Br)[N:20]4[C:25]=3[C:24]([NH2:26])=[N:23][CH:22]=[N:21]4)[CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[ClH:31].FC1(F)CCNC1.C(N(CC)CC)C.[I-].[Na+]>CN(C=O)C>[CH2:1]([N:8]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17]3[CH:18]=[C:19]([CH2:27][CH2:28][CH2:29][Cl:31])[N:20]4[C:25]=3[C:24]([NH2:26])=[N:23][CH:22]=[N:21]4)[CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 249034823,3-Difluoropyrrolidine hydrochlorideHCID 58529276HCID 58529276, compound

Product 1

HCID 58529569HCID 58529569, compoundYield 20.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-(2-benzyl-2H-indazol-6-yl)-7-(3-bromopropyl)pyrrolo[2,1-f][1,2,4]-triazin-4-ylamine (50 mg, 0.108 mmol), 3,3-difluoropyrrolidine hydrochloride (78 mg, 0.54 mmol, 5.0 eq), triethylamine (77 mg, 0.76 mmol, 7.0 eq), and sodium iodide (3.3 mg, 0.022 mmol, 0.2 eq) in anhydrous DMF (1.0 mL) was stirred at 50° C. for 6 h. The reaction mixture was partitioned between EtOAc and water, and the organic layer was washed with 50% aq. brine (3×), dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was dissolved in MeOH (3 mL) and purified using HPLC (RT=10.16 min) to give a colorless oil. Crystallization from DCM/hexane afforded 9.4 mg (20.8%) of the byproduct as a white solid. 1H-NMR (CD3OD) 8.35 (s, 1H), 7.82 (s, 1H), 7.81 (d, 1H), 7.64 (s, 1H), 7.36 to 7.30 (m, 5H), 7.23 (d, 1H), 6.62 (s, 1H), 5.66 (s, 2H), 3.64 (t, 2H), 3.14 (t, 2H), 226 to 2.22 (m, 2H); LC-MS [M+H]+=417/419, RT=2.91 min.

Workup

  1. customThe reaction mixture was partitioned between EtOAc and water
  2. washthe organic layer was washed with 50% aq. brine (3×)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe crude product was dissolved in MeOH (3 mL)
  7. custompurified
  8. customto give a colorless oil
  9. customCrystallization from DCM/hexane

Sources & evidence

ORD record
ord-5033f63f5f7f43d7b6029cbe02475cba
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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