N,N-Dimethylglycine → HCID 58529288, compound

HRID 1972910Notes

Reaction equation

HRID 1972910 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](C4CCNCC4)[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.[CH3:33][N:34]([CH3:39])[CH2:35][C:36](O)=[O:37].CCN=C=NCCCN(C)C.Cl.[CH:52]1[CH:53]=[CH:54]C2N(O)N=[N:58][C:56]=2[CH:57]=1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH2:1]([N:8]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17]3[CH:18]=[C:19]([CH:53]4[CH2:52][CH2:57][CH2:56][N:58]([C:36](=[O:37])[CH2:35][N:34]([CH3:39])[CH3:33])[CH2:54]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:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 673N,N-DimethylglycineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 16066662HCID 16066662, compound

Product 1

HCID 58529288HCID 58529288, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-(2-benzyl-2H-indazol-6-yl)-7-piperidin-4-ylpyrrolo[2,1-f][1,2,4]triazin-4-amine (100 mg, 0.24 mmol), N,N-dimethylglycine (29 mg, 0.28 mmol), EDCl (50 mg, 0.26 mmol), HOBt (35 mg, 0.26 mmol), and N,N-diisopropylethylamine (123 μL, 0.71 mmol) in DMF (1.5 mL) was stirred at rt for 16 h. The Prude mixture 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 24 mg (20%) of the desired product 1H NMR (400 MHz, DMSO-d6) δ 8.54 (s, 1 H), 7.91 (d, 1 H), 7.80 (d, 1 H), 7.58 (s, 1 H), 7.26-7.41 (m, 5 H), 7.13 (d, 1 H), 6.64 (d, 1 H), 5.65 (s, 2 H), 4.44 (dd, 1 H), 4.13 (dd, 1 H), 2.61-3.68 (m, 5 H), 2.22 (s, 3 H), 2.16 (s, 3 H), 1.68-1.94 (m, 1 H), 1.39-1.65 (m, 1 H); ES-MS m/z 509.36 [M+H]+, HPLC RT (min) 2.54.

Workup

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

Sources & evidence

ORD record
ord-7cfc6e1956d54bb9af45a73a0bab7aec
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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