Triethylamine → HCID 58529453, compound

HRID 1972935Notes

Reaction equation

HRID 1972935 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][CH:30]=[C:29]([CH2:33]Br)[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.[NH:35]1[CH2:39][CH2:38][CH:37]([OH:40])[CH2:36]1.C(N(CC)CC)C>CN(C=O)C.[I-].[Na+]>[NH2:26][C:24]1[C:25]2=[C:17]([C:12]3[CH:11]=[CH:10][C:15]4[C:14]([CH:13]=3)=[N:9][N:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:16]=4)[CH:18]=[C:19]([C:27]3[CH:28]=[C:29]([CH:30]=[CH:31][CH:32]=3)[CH2:33][N:35]3[CH2:39][CH2:38][CH:37]([OH:40])[CH2:36]3)[N:20]2[N:21]=[CH:22][N:23]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 982104-HydroxypyrrolidineHCID 58529780HCID 58529780, compound

Product 1

HCID 58529453HCID 58529453, compoundYield 22.1%

Reagents, catalysts & solvents 2

HCID 5238Sodium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of 5-(2-benzyl-2H-indazol-6-yl)-7-[3-(bromomethyl)phenyl]pyrrolo[2,1-f][1,2,4]triazin-4-amine (125 mg, 025 mmol) in DMF (1 mL) was added 3-pyrrolidinol (26 μL, 0.27 mmol), triethylamine (103 μl, 0.74 mmol), and sodium iodide (0.4 mg, 0.002 mmol). The reaction was heated (55° C.) for 17 h and then cooled to rt. The crude reaction mixture was purified via preparative HPLC using a gradient elution from 15% to 50% 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 28 mg (22%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 8.57 (s, 1 H), 7.92-8.00 (m, 3 H), 7.83 (d, 1 H), 7.69 (d, 1 H), 7.25-7.44 (m, 7 H), 7.22 (dd, 1 H), 7.14 (s, 1 H), 5.67 (s, 2 H), 4.68 (d, 1 H), 4.09-4.21 (m, 1 H), 3.60 (q, 2 H), 2.65-2.72 (m, 1 H), 2.58 (q, 1 H), 2.37-2.46 (m, 1 H), 2.32 (dd, 1 H), 1.93-2.03 (m, 1 H), 1.48-1.59 (m, 1 H); ES-MS m/z 516.20 [M+H]+, HPLC RT (min) 2.53.

Workup

  1. temperaturecooled to rt
  2. customThe crude reaction mixture
  3. customwas purified via preparative HPLC
  4. washa gradient elution from 15% to 50% acetonitrile in water
  5. filtrationfollowed by filtration through an acidic resin
  6. washwashing with MeOH
  7. washThe product was eluted with 2M NH3 in MeOH
  8. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-6d283779f0ec4e0ab90731045bf50d00
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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