N,N-Dimethylglycine → HCID 71134321, compound

HRID 1972938Notes

Reaction equation

HRID 1972938 reaction equation
Cl.[CH2:2]([N:9]1[CH:17]=[C:16]2[C:11]([CH:12]=[C:13]([C:18]3[CH:19]=[C:20]([C:28]4[N:29]=[C:30]([CH:33]5[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]5)[S:31][CH:32]=4)[N:21]4[C:26]=3[C:25]([NH2:27])=[N:24][CH:23]=[N:22]4)[CH:14]=[CH:15]2)=[N:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:39][N:40]([CH3:45])[CH2:41][C:42](O)=[O:43].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>[CH2:2]([N:9]1[CH:17]=[C:16]2[C:11]([CH:12]=[C:13]([C:18]3[CH:19]=[C:20]([C:28]4[N:29]=[C:30]([CH:33]5[CH2:38][CH2:37][N:36]([C:42](=[O:43])[CH2:41][N:40]([CH3:45])[CH3:39])[CH2:35][CH2:34]5)[S:31][CH:32]=4)[N:21]4[C:26]=3[C:25]([NH2:27])=[N:24][CH:23]=[N:22]4)[CH:14]=[CH:15]2)=[N:10]1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

7

Reactant 5

HCID 673N,N-DimethylglycineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 69302734HCID 69302734, compound

Product 1

HCID 71134321HCID 71134321, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-(2-benzyl-2H-indazol-6-yl)-7-(2-piperidin-4-yl-1,3-thiazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine hydrochloride (100 mg, 0.17 mmol), N,N-dimethylglycine (19 mg, 0.18 mmol), EDCl (36 mg, 0.19 mmol), HOBt (26 mg, 0.19 mmol), and N,N-diisopropylethylamine (90 μL, 0.52 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 20 mg (20%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 8.56 (s, 1 H), 8.37 (s, 1 H), 8.09 (s, 1 H), 7.82 (d, 1 H), 7.67 (s, 1 H), 7.26-7.39 (m, 5H), 7.16-7.23 (m, 2 H), 5.66 (s, 2 H), 4.40 (d, 1 H), 4.10 (d, 1 H), 3.01-3.23 (m, 3 H), 2.75 (t, 1 H), 2.18 (s, 6H), 2.06-2.15 (m, 3 H), 1.70 (q, 1 H), 1.53 (q, 1 H); ES-MS m/z 592.16 HPLC RT (min) 2.39.

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-af2dd3b88e7046f6a97d4bf28e615702
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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