Formaldehyde → 5-(2-benzyl-2H-indazol-6-yl)-7-(4-(4-methylpiperazin-1-yl)phenyl]pyrrolo[2,1-f][1,2,4]triazin-4-amine

HRID 1972772Notes

Reaction equation

HRID 1972772 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]([C:27]4[CH:32]=[CH:31][C:30]([N:33]5[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]5)=[CH:29][CH:28]=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.C=O.[C:41](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[CH2:1]([N:8]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17]3[CH:18]=[C:19]([C:27]4[CH:32]=[CH:31][C:30]([N:33]5[CH2:38][CH2:37][N:36]([CH3:41])[CH2:35][CH2:34]5)=[CH:29][CH:28]=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

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 585294985-(2-benzyl-2H-indazol-6-yl)-7-(4-piperazin-1-ylphenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine

Product 1

HCID 585295775-(2-benzyl-2H-indazol-6-yl)-7-(4-(4-methylpiperazin-1-yl)phenyl]pyrrolo[2,1-f][1,2,4]triazin-4-amineYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 5-(2-benzyl-2H-indazol-6-yl)-7-(4-piperazin-1-ylphenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (89 mg, 0.18 mmol) in dichloromethane (3 mL) was added formaldehyde (37% in water) (80 μL, 1.06 mmol) and sodium triacetoxyborohydride (113 mg, 0.53 mmol). The reaction was stirred (rt) for 17 h. The mixture was diluted with dichloromethane (25 mL) and was washed with H2O (1×20 mL), brine, and was dried (Na2SO4) and evaporated. The residue was purified by preparative HPLC using a gradient elution from 5% to 30% acetonitrile in water to obtain 53 mg (58%) of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 8.57 (s, 1 H), 7.99-7.91 (m, 3 H), 7.86-7.79 (m, 1 H), 7.69-7.63 (m, 1 H), 7.39-7.26 (m, 5 H), 7.23-7.17 (m, 1 H), 7.06-6.98 (m, 3 H), 5.66 (s, 2 H), 3.27-3.14 (m, 4 H), 2.47-2.40 (m, 4 H), 2.22 (s, 3 H); ES-MS m/z 515.32 [M+H]+, HPLC RT (min) 2.36.

Workup

  1. washwas washed with H2O (1×20 mL), brine
  2. dry with materialwas dried (Na2SO4)
  3. customevaporated
  4. customThe residue was purified by preparative HPLC
  5. washa gradient elution from 5% to 30% acetonitrile in water

Sources & evidence

ORD record
ord-9df24552ce504261a8cb6cc2da501b68
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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