N,N-Dimethylglycine → HCID 58529324, compound

HRID 1972916Notes

Reaction equation

HRID 1972916 reaction equation
[CH2:1]([N:8]1[C:16]([CH3:17])=[C:15]2[C:10]([CH:11]=[C:12]([C:18]3[CH:19]=[C:20]([CH:28]4[CH2:33][CH2:32][CH2:31][NH:30][CH2:29]4)[N:21]4[C:26]=3[C:25]([NH2:27])=[N:24][CH:23]=[N:22]4)[CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:34][N:35]([CH3:40])[CH2:36][C:37](O)=[O:38].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>[CH2:1]([N:8]1[C:16]([CH3:17])=[C:15]2[C:10]([CH:11]=[C:12]([C:18]3[CH:19]=[C:20]([CH:28]4[CH2:33][CH2:32][CH2:31][N:30]([C:37](=[O:38])[CH2:36][N:35]([CH3:40])[CH3:34])[CH2:29]4)[N:21]4[C:26]=3[C:25]([NH2:27])=[N:24][CH:23]=[N:22]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 58529603HCID 58529603, compound

Product 1

HCID 58529324HCID 58529324, compoundYield 16%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-(2-benzyl-3-methyl-2H-indazol-6-yl)-7-piperidin-3-ylpyrrolo[2,1-f][1,2,4]triazin-4-amine (100 mg, 0.23 mmol), N,N-dimethylglycine (28 mg, 0.27 mmol), EDCl (48 mg, 0.25 mmol), HOBt (34 mg, 0.25 mmol), and N,N-diisopropylethylamine (119 μL, 0.69 mmol) in DMF (1.5 mL) was stirred at rt for 16 h. The crude 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 19 mg (16%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 7.92 (d, 1 H), 7.76 (d, 1 H), 7.53 (s, 1 H), 7.25-7.38 (m, 3 H), 7.21 (d, 2 H), 7.08 (d, 1 H), 6.63-6.68 (m, 1 H), 5.63 (s, 2 H), 3.96-4.95 (m, 2 H), 2.83-3.34 (m, 5 H), 2.57-2.77 (m, 4 H), 2.06-2.23 (m, 6 H), 1.69-1.92 (m, 2 H), 1.39-1.64 (m, 1 H); ES-MS m/z 523.41 [M+H]+, HPLC RT (min) 2.20.

Workup

  1. customThe crude 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-f68ac5c028b645939daf7c4443757042
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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