Dimethylformamide → HCID 57731453, compound

HRID 2234717Notes

Reaction equation

HRID 2234717 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[CH:23]=[CH:22][C:21]([NH:24][C:25]([N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[O:26])=[C:20]([C:33]([N:35]4[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]4)=[O:34])[CH:19]=3)[CH:16]=2)[N:11](S(C2C=CC(C)=CC=2)(=O)=O)[CH:10]=1.CN(C)C=O.[OH-].[K+]>CO>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[CH:23]=[CH:22][C:21]([NH:24][C:25]([N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[O:26])=[C:20]([C:33]([N:35]4[CH2:36][CH2:37][N:38]([CH3:41])[CH2:39][CH2:40]4)=[O:34])[CH:19]=3)[CH:16]=2)[NH:11][CH:10]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 14797Potassium HydroxideHCID 57731554HCID 57731554, compound

Product 1

HCID 57731453HCID 57731453, compoundYield 21.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Crude morpholine-4-carboxylic acid [4-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-2-(4-methyl-piperazine-1-carbonyl)-phenyl]-amide (0.637 mmol) was dissolved in methanol (1.0 mL) and dimethylformamide (1.0 mL) and 50% w/v aqueous potassium hydroxide (1.0 mL) was added. After 2 hours, the reaction was quenched by addition of acetic acid (1.0 mL). The mixture was carefully poured into saturated sodium bicarbonate and extracted with ethyl acetate. The organic layers were dried over sodium sulfate, filtered and dried to a residue which was purified by preparative HPLC to afford morpholine-4-carboxylic acid [4-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-2-(4-methyl-piperazine-1-carbonyl)-phenyl]-amide (74.5 mg, 21.0%, 4 steps). 1H-NMR (500 MHz, dimethylsulfoxide-d6) δ 2.18 (s, 3H), 2.31 (br m, 4H), 3.38 (t, J=4.5 Hz, 1H), 3.61 (t, J=5.0 Hz, 1H), 3.82 (s, 3H), 7.05 (dt, J=7.5, J=1.0 Hz, 1H), 7.12 (d, J=7.5 Hz, 1H), 7.29 (dd, J=1.5, J=9.0 Hz 1H), 7.54 (d, J=2.0 Hz, 1H), 7.60 (dd, J=1.5 Hz, J=7.0 Hz, 1H), 7.60 (d, J=9.0, 1H), 7.72 (m, 2H), 8.14 (d, J=1.5 Hz, 1H), 8.53 (d, J=2.0, 1H), 8.60 (s, 1H), 11.9 (s, 1H). MS: m/z 556 (M+H+).

Workup

  1. additionwas added
  2. customthe reaction was quenched by addition of acetic acid (1.0 mL)
  3. additionThe mixture was carefully poured into saturated sodium bicarbonate
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. customdried to a residue which
  8. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-57e768a898c84428851582584b91f9f5
Source dataset
uspto-grants-2010_05
Patent number
US07709645B2

Reaction notes

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