Dimethylamine → 3-(1,1-Dioxothiomorpholin-4-yl)-3-{3-[3-(2-methoxy-phenyl)-1h-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-n,n-dimethyl-propionamide

HRID 886564Notes

Reaction equation

HRID 886564 reaction equation
[O:1]=[S:2]1(=O)[CH2:7][CH2:6][N:5]([CH:8]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]3[CH:20]=[C:21]4[C:27]([C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=5[O:34][CH3:35])=[CH:26][N:25](S(C5C=CC(C)=CC=5)(=O)=O)[C:22]4=[N:23][CH:24]=3)[CH:14]=2)[CH2:9][C:10](O)=[O:11])[CH2:4][CH2:3]1.[CH3:47][NH:48][CH3:49].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[OH-:83].[K+]>CN(C=O)C.CO>[O:83]=[S:2]1(=[O:1])[CH2:3][CH2:4][N:5]([CH:8]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]3[CH:20]=[C:21]4[C:27]([C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=5[O:34][CH3:35])=[CH:26][NH:25][C:22]4=[N:23][CH:24]=3)[CH:14]=2)[CH2:9][C:10]([N:48]([CH3:49])[CH3:47])=[O:11])[CH2:6][CH2:7]1

Participants

8

Reactant 5

HCID 674DimethylamineHCID 14797Potassium HydroxideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 598250103-(1,1-dioxothiomorpholin-4-yl)-3-{3-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-propionic acid

Product 1

HCID 251564633-(1,1-Dioxothiomorpholin-4-yl)-3-{3-[3-(2-methoxy-phenyl)-1h-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-n,n-dimethyl-propionamideYield 39%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(1,1-dioxothiomorpholin-4-yl)-3-{3-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-propionic acid (100 mg, 0.15 mmol), dimethylamine (2 N solution in THF, 0.15 mL, 0.30 mmol), diisopropylethylamine (23 mg, 0.18 mmol) in DMF (1 mL) was added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (68 mg, 0.18 mmol). The resulting solution was stirred at room temperature for 1 hour. Methanol (1 mL) and potassium hydroxide (50% w/v in water, 0.2 mL) were added and the resulting mixture was stirred for 30 minutes. The mixture was directly purified by mass-triggered reverse-phase HPLC to afford 3-(1,1-dioxothiomorpholin-4-yl)-3-{3-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-N,N-dimethyl-propionamide as a white solid (31 mg, 39%). MS: m/z 533 (M+H+). 1H NMR (500 MHz, DMSO-d6) δ 2.75 (s, 3H), 2.82 (br, 2H), 2.88 (dd, 1H), 2.96 (br, 2H), 3.02 (s, 3H), 3.07 (br, 4H), 3.105 (dd, 1H), 3.83 (s, 3H), 4.41 (br, 1H), 7.05 (t, 1H), 7.15 (d, 1H), 7.30 (t, 1H), 7.30 (dt, 1H), 7.31 (d, 1H), 7.44 (t, 1H), 7.61 (d, 1H), 7.65 (s, 1H), 7.74 (d, 1H), 8.18 (d, 1H), 8.57 (d, 1H), 11.93 (s, 1H).

Workup

  1. stirringthe resulting mixture was stirred for 30 minutes
  2. customThe mixture was directly purified by mass-triggered reverse-phase HPLC

Sources & evidence

ORD record
ord-405b795280934910a62d1645ac992b0b
Source dataset
uspto-grants-2012_08
Patent number
US08242280B2

Reaction notes

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