1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (R)-2-((1-(2-(3,5-dichlorophenylamino)acetyl)piperidin-3-yl)(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl) amino)-N,N-dimethylacetamide

HRID 919576Notes

Reaction equation

HRID 919576 reaction equation
[CH3:1][N:2]([CH3:32])[C:3](=[O:31])[CH2:4][N:5]([C@@H:25]1[CH2:30][CH2:29][CH2:28][NH:27][CH2:26]1)[C:6]1[C:7]2[CH:14]=[CH:13][N:12]([S:15]([C:18]3[CH:24]=[CH:23][C:21]([CH3:22])=[CH:20][CH:19]=3)(=[O:17])=[O:16])[C:8]=2[N:9]=[CH:10][N:11]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[Cl:54][C:55]1[CH:56]=[C:57]([NH:62][CH2:63][C:64](O)=[O:65])[CH:58]=[C:59]([Cl:61])[CH:60]=1.CCN(C(C)C)C(C)C>CN(C=O)C.O>[Cl:54][C:55]1[CH:56]=[C:57]([NH:62][CH2:63][C:64]([N:27]2[CH2:28][CH2:29][CH2:30][C@@H:25]([N:5]([C:6]3[C:7]4[CH:14]=[CH:13][N:12]([S:15]([C:18]5[CH:19]=[CH:20][C:21]([CH3:22])=[CH:23][CH:24]=5)(=[O:17])=[O:16])[C:8]=4[N:9]=[CH:10][N:11]=3)[CH2:4][C:3]([N:2]([CH3:1])[CH3:32])=[O:31])[CH2:26]2)=[O:65])[CH:58]=[C:59]([Cl:61])[CH:60]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 13138167(3,5-Dichlorophenyl)glycineHCID 86706454(R)-N, N-dimethyl-2-(piperidin-3-yl(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino) acetamide

Product 1

HCID 86706453(R)-2-((1-(2-(3,5-dichlorophenylamino)acetyl)piperidin-3-yl)(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl) amino)-N,N-dimethylacetamideYield 31.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (R)—N, N-dimethyl-2-(piperidin-3-yl(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino) acetamide (100 mg, 0.24 mmol) in DMF (7 mL) was added EDCI (54 mg, 0.3 mmol), HOBt (39 mg, 0.3 mmol), 2-(3,5-dichlorophenylamino)acetic acid (53 mg, 0.24 mmol) and DIEA (0.50 mL, 0.36 mmol) at 0° C. The solution was stirred at rt overnight and the reaction mixture was diluted with water (50 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo to give a residue which was purified by column chromatography (silica gel, gradient 0-2% methanol in chloroform) to afford the titled compound (50 mg, 31%). LCMS [M+1]: 675.

Workup

  1. dry with materialThe organic layer was dried (Na2SO4)
  2. concentrationconcentrated in vacuo
  3. customto give a residue which
  4. customwas purified by column chromatography (silica gel, gradient 0-2% methanol in chloroform)

Sources & evidence

ORD record
ord-c035a5572a414cde963096d5487360b0
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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