Sodium Iodide → HCID 58529356, compound

HRID 1972894Notes

Reaction equation

HRID 1972894 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][C:28]4[CH:37]=[C:36]5[C:31]([CH2:32][CH2:33][NH:34][CH2:35]5)=[CH:30][CH:29]=4)[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.Br[CH2:39][CH2:40][O:41][Si](C(C)(C)C)(C)C.C(N(CC)CC)C.[I-].[Na+]>CN(C=O)C>[NH2:26][C:24]1[C:25]2=[C:17]([C:12]3[CH:13]=[CH:14][C:15]4[C:10]([CH:11]=3)=[N:9][N:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:16]=4)[CH:18]=[C:19]([CH2:27][C:28]3[CH:37]=[C:36]4[C:31]([CH2:32][CH2:33][N:34]([CH2:39][CH2:40][OH:41])[CH2:35]4)=[CH:30][CH:29]=3)[N:20]2[N:21]=[CH:22][N:23]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 58529408HCID 58529408, compound

Product 1

HCID 58529356HCID 58529356, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

5-(2-Benzyl-2H-indazol-6-yl)-7-(1,2,3,4-tetrahydro-isoquinolin-7-ylmethyl)-pyrrolo[2,1-f][1,2,4]triazin-4-ylamine (200 mg, 0.41 mmol) was dissolved in DMF (4 mL) and (2-bromo-ethoxy)-tert-butyl-dimethyl-silane (0.15 g, 0.62 mmol) was added followed by triethylamine (0.17 mL, 1.26 mmol) and sodium iodide (0.006 g, 0.004 mmol). The resulting mixture was stirred at 50° C. overnight. The mixture was concentrated, dried using a vacuum pump for 2 hours. The residue was dissolved in 2 mL dichloromethane and TFA (0.30 mL) was added and the resulting solution was stirred overnight, concentrated and purified by preparative HPLC to afford 32 mg (15%) of the title compound. 1H-NMR (CD3OD-d4) 8.36-8.33 (m, 1 H), 7.81 (s, 1 H), 7.76 (dd, 1H), 7.63-7.61 (m, 1 H), 7.38-7.29 (m, 5 H), 7.19 (dd, 1 H), 7.11-6.98 (m, 3 H), 6.46 (s, 1 H), 5.65 (s, 2 H), 4.24 (s, 2 H), 3.76 (t, 2 H), 3.67 (s, 2 H), 2.93-2.79 (m, 4 H), 2.69 (t, 2 H); LC-MS [M+H]+=530.3, RT=2.36 min.

Workup

  1. concentrationThe mixture was concentrated
  2. customdried
  3. customfor 2 hours
  4. dissolutionThe residue was dissolved in 2 mL dichloromethane
  5. additionTFA (0.30 mL) was added
  6. stirringthe resulting solution was stirred overnight
  7. concentrationconcentrated
  8. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-bd144329d3624423a13c1c770766aca8
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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