Acetic Acid → HCID 58529679, compound

HRID 1972939Notes

Reaction equation

HRID 1972939 reaction equation
Cl.[CH2:2]([N:9]1[CH:17]=[C:16]2[C:11]([CH:12]=[C:13]([C:18]3[CH:19]=[C:20]([C:28]4[N:29]=[C:30]([CH:33]5[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]5)[S:31][CH:32]=4)[N:21]4[C:26]=3[C:25]([NH2:27])=[N:24][CH:23]=[N:22]4)[CH:14]=[CH:15]2)=[N:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.CC(O)=O.C(O[C:46]1(O[Si](C)(C)C)[CH2:48][CH2:47]1)C.C([BH3-])#N.[Na+].[OH-].[Na+]>CO>[CH2:2]([N:9]1[CH:17]=[C:16]2[C:11]([CH:12]=[C:13]([C:18]3[CH:19]=[C:20]([C:28]4[N:29]=[C:30]([CH:33]5[CH2:38][CH2:37][N:36]([CH:46]6[CH2:48][CH2:47]6)[CH2:35][CH2:34]5)[S:31][CH:32]=4)[N:21]4[C:26]=3[C:25]([NH2:27])=[N:24][CH:23]=[N:22]4)[CH:14]=[CH:15]2)=[N:10]1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 69302734HCID 69302734, compound

Product 1

HCID 58529679HCID 58529679, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 5-(2-benzyl-2H-indazol-6-yl)-7-(2-piperidin-4-yl-1,3-thiazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine hydrochloride (100 mg, 0.17 mmol) in MeOH (2 mL) containing 3 Å molecular sieves was added AcOH (99 μL, 1.73 mmol), [(1-ethoxycyclopropyl)oxy]trimethylsilane (180 mg, 1.04 mmol) and sodium cyanoborohydride (49 mg, 0.78 mmol). The reaction was stirred at 60° C. for 17 h. Aqueous NaOH (1N, 5 mL) was added and the mixture was extracted with EtOAc (2×10 mL). The combined organic layers were washed with brine, dried (Na2SO4) and concentrated. The residue was purified by preparative HPLC using a gradient elution from 15% to 45% 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 19 mg (21%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 8.57 (s, 1 H), 8.35 (s, 1 H), 8.09 (s, 1 H), 7.83 (d, 1 H), 7.67 (s, 1 H), 7.28-7.41 (m, 5H), 7.18-7.23 (m, 2 H), 5.67 (s, 2 H), 2.95-3.09 (m, 3 H), 2.30 (t, 2 H), 2.05 (d, 2 H), 1.57-1:72 (m, 3 H), 0.37-0.45 (m, 2 H), 0.25-0.34 (m, 2 H); ES-MS m/z 547.21 HPLC RT (min) 2.39.

Workup

  1. extractionthe mixture was extracted with EtOAc (2×10 mL)
  2. washThe combined organic layers 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 45% 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-e2a9b2759f92405aa177487ab8529a45
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

Loading…