N,N-Dimethylglycine → HCID 58529784, compound

HRID 1972948Notes

Reaction equation

HRID 1972948 reaction equation
[NH:1]1[CH2:4][CH:3]([C:5]2[N:13]3[C:8]([C:9]([NH2:14])=[N:10][CH:11]=[N:12]3)=[C:7]([C:15]3[CH:16]=[CH:17][C:18]4[C:22]([CH:23]=3)=[N:21][N:20]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:19]=4)[CH:6]=2)[CH2:2]1.[CH3:31][N:32]([CH3:37])[CH2:33][C:34](O)=[O:35].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH2:24]([N:20]1[CH:19]=[C:18]2[C:22]([CH:23]=[C:15]([C:7]3[CH:6]=[C:5]([CH:3]4[CH2:4][N:1]([C:34](=[O:35])[CH2:33][N:32]([CH3:37])[CH3:31])[CH2:2]4)[N:13]4[C:8]=3[C:9]([NH2:14])=[N:10][CH:11]=[N:12]4)[CH:16]=[CH:17]2)=[N:21]1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

7

Reactant 5

HCID 673N,N-DimethylglycineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58529976HCID 58529976, compound

Product 1

HCID 58529784HCID 58529784, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 7-azetidin-3-yl-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (20 mg, 0.051 mmol), N,N-dimethylglycine (5.7 mg, 0.056 mmol), EDCl (11.6 mg, 0.061 mmol), HOBt (8.2 mg, 0.061 mmol), and N,N-diisopropylethylamine (26 μL, 0.15 mmol) in DMF (1 mL) was stirred at rt for 16 h. The crude reaction mixture was purified via 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 5 mg (21%) of the desired product. 1H NMR (400 MHz, CD3OD) δ 8.37 (s, 1 H), 7.79-7.85 (m, 2 H), 7.67 (s, 1 H), 7.29-7.37 (m, 5 H), 7.25 (d, 1 H), 6.81 (s, 1 H), 5.65 (s, 2 H), 4.70 (t, 1 H), 4.25-4.54 (m, 4 H), 3.18 (s, 2 H), 2.38 (s, 6 H); ES-MS m/z 481.10 [M+H]+, HPLC RT (min) 2.07.

Workup

  1. customThe crude reaction mixture
  2. customwas purified via preparative HPLC
  3. washa gradient elution from 15% to 45% acetonitrile in water
  4. filtrationfollowed by filtration through an acidic resin
  5. washwashing with MeOH
  6. washThe product was eluted with 2M NH3 in MeOH
  7. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-aa9b35ce41d0483386f74f2a0b43c378
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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