Dimethylamine → HCID 57537636, compound

HRID 1693738Notes

Reaction equation

HRID 1693738 reaction equation
Cl[C:2]1[C:7]([C:8]2[CH:9]=[C:10]([CH:14]([OH:20])[C:15]([N:17]([CH3:19])[CH3:18])=[O:16])[CH:11]=[N:12][CH:13]=2)=[CH:6][N:5]=[C:4]2[N:21](COCC[Si](C)(C)C)[CH:22]=[C:23]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[O:30][CH3:31])[C:3]=12.[CH3:40][NH:41][CH3:42].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.Cl.CNC.C(N(CC)C(C)C)(C)C>O1CCOCC1.CN(C=O)C>[CH3:40][N:41]([CH3:42])[C:2]1[C:7]([C:8]2[CH:9]=[C:10]([CH:14]([OH:20])[C:15]([N:17]([CH3:18])[CH3:19])=[O:16])[CH:11]=[N:12][CH:13]=2)=[CH:6][N:5]=[C:4]2[NH:21][CH:22]=[C:23]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[O:30][CH3:31])[C:3]=12

Participants

8

Reactant 5

HCID 674DimethylamineHCID 10473Dimethylamine, hydrochlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57537513HCID 57537513, compound

Product 1

HCID 57537636HCID 57537636, compoundYield 1.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

2-{5-[4-Chloro-3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyridin-3-yl}-2-hydroxy-N,N-dimethyl-acetamide (18 mg, 0.317 mmol) was dissolved in a solution of dimethyl amine (2 mL, 17.7 mmol) and 1,4 dioxane (1 mL). The mixture was heated for at 150° C. for 15 hours in a sealed vessel and concentrated under in vacuo. To the residue were added O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (14.5 mg, 0.0381 mmol), dimethylamine hydrochloride salt (12 mg, 0.147 mmol), N,N-dimethylformaldehyde and N,N-Diisopropylethylamine (33 μL, 0.317 mmol). After stirring at 23° C. for 1 hour, the mixture was concentrated. The crude product was dissolved in 1 mL TFA and stirred at 23° C. for 1 hour. The solvent was evaporated and the resulting oil was dissolved in 1 mL DMSO and 50 μL ethylenediamine and purified by mass triggered reverse phase HPLC to afford 2-{5-[4-Dimethylamino-3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyridin-3-yl}-2-hydroxy-N,N-dimethyl-acetamide (1.60 mg, 0.00359 mmol, 1.1% yield). 1H-NMR [500 MHz, d6-DMSO] δ: 8.56 (d, 2H), 7.99 (s, 1H), 7.63 (s, 1H), 7.32 (m, 1H), 7.24 (dd, 1H), 7.04 (d, 1H), 6.97 (t, 1H), 5.57 (s, 1H) 3.68 (s, 4H), 2.95 (s, 4H), 2.82 (s, 3H), 2.18 (s, 6H); MS [MH+] m/z: 446.

Workup

  1. concentrationconcentrated under in vacuo
  2. concentrationthe mixture was concentrated
  3. dissolutionThe crude product was dissolved in 1 mL TFA
  4. stirringstirred at 23° C. for 1 hour
  5. customThe solvent was evaporated
  6. dissolutionthe resulting oil was dissolved in 1 mL DMSO
  7. custom50 μL ethylenediamine and purified by mass triggered reverse phase HPLC

Sources & evidence

ORD record
ord-edef178e38b3422c88a02a4ceb07e3f9
Source dataset
uspto-grants-2012_04
Patent number
US08158647B2

Reaction notes

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