Acetic Acid → HCID 58529866, compound

HRID 1972928Notes

Reaction equation

HRID 1972928 reaction equation
[NH:1]1[CH2:7][CH2:6][CH2:5][CH:4]([C:8]2[N:16]3[C:11]([C:12]([NH2:17])=[N:13][CH:14]=[N:15]3)=[C:10]([C:18]3[CH:19]=[CH:20][C:21]4[C:25]([CH:26]=3)=[N:24][N:23]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:22]=4)[CH:9]=2)[CH2:3][CH2:2]1.CC(O)=O.C(O[C:41]1(O[Si](C)(C)C)[CH2:43][CH2:42]1)C.C([BH3-])#N.[Na+].[OH-].[Na+]>CO>[CH2:27]([N:23]1[CH:22]=[C:21]2[C:25]([CH:26]=[C:18]([C:10]3[CH:9]=[C:8]([CH:4]4[CH2:5][CH2:6][CH2:7][N:1]([CH:41]5[CH2:43][CH2:42]5)[CH2:2][CH2:3]4)[N:16]4[C:11]=3[C:12]([NH2:17])=[N:13][CH:14]=[N:15]4)[CH:19]=[CH:20]2)=[N:24]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 58529755HCID 58529755, compound

Product 1

HCID 58529866HCID 58529866, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 7-azepan-4-yl-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (100 mg, 0.20 mmol) in MeOH (2 mL) containing 3 Å molecular sieves was added AcOH (112 μL, 2.00 mmol), [(1-ethoxycyclopropyl)oxy]trimethylsilane (236 μL, 1.18 mmol) and sodium cyanoborohydride (55 mg, 0.88 mmol). The reaction was stirred at 60° C. for 17 h. Aqueous NaOH (1N, 15 mL) was added and the mixture was extracted with EtOAc (3×15 mL). The combined organics were washed with brine, dried (Na2SO4) and concentrated. The residue was purified by preparative HPLC using a gradient elution from 15% to 40% acetonitrile in water followed by filtration through an acidic resin, washing with MeOH. The product was eluted with 2M NH3 in MeOH and the filtrate was concentrated to provide 47 mg (50%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 8.23 (s, 1 H), 7.58 (s, 1 H), 7.48 (d, 1 H), 7.28 (s, 1 H), 6.97-7.07 (m, 5 H), 6.84 (dd, 1 H), 6.27 (s, 1 H), 5.34 (s, 2 H), 3.04-3.15 (m, 1 H), 2.56-2.64 (m, 1 H), 2.44-2.53 (m, 2 H), 1.27-1.77 (m, 6 H), 0.07-0.14 (m, 2 H), −0.03-0.05 (m, 2 H); ES-MS m/z 478.33 [M+H]+, HPLC RT (min) 2.10.

Workup

  1. extractionthe mixture was extracted with EtOAc (3×15 mL)
  2. washThe combined organics were washed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was purified by preparative HPLC
  6. washa gradient elution from 15% to 40% acetonitrile in water
  7. filtrationfollowed by filtration through an acidic resin
  8. washwashing with MeOH
  9. washThe product was eluted with 2M NH3 in MeOH
  10. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-046f2fe34a2e4b0fa1f2b4a3baee16c0
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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