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

HRID 919574Notes

Reaction equation

HRID 919574 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([N:7]([C:11]2[C:12]3[CH:19]=[CH:18][N:17]([S:20]([C:23]4[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=4)(=[O:22])=[O:21])[C:13]=3[N:14]=[CH:15][N:16]=2)[CH2:8][CH2:9][OH:10])[CH2:2]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[Cl:51][C:52]1[CH:53]=[C:54]([NH:59][CH2:60][C:61](O)=[O:62])[CH:55]=[C:56]([Cl:58])[CH:57]=1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[Cl:51][C:52]1[CH:53]=[C:54]([NH:59][CH2:60][C:61]([N:1]2[CH2:6][CH2:5][CH2:4][C@@H:3]([N:7]([CH2:8][CH2:9][OH:10])[C:11]3[C:12]4[CH:19]=[CH:18][N:17]([S:20]([C:23]5[CH:24]=[CH:25][C:26]([CH3:27])=[CH:28][CH:29]=5)(=[O:21])=[O:22])[C:13]=4[N:14]=[CH:15][N:16]=3)[CH2:2]2)=[O:62])[CH:55]=[C:56]([Cl:58])[CH:57]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 13138167(3,5-Dichlorophenyl)glycineHCID 69676526(R)-2-(piperidin-3-yl(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethanol

Product 1

HCID 69676522(R)-2-(3,5-dichlorophenylamino)-1-(3-((2-hydroxyethyl)(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)ethanoneYield 30%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (R)-2-(piperidin-3-yl(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethanol (0.9 mg, 2.2 mmol) in DMF (10 mL) was added EDCI (494 mg, 2.6 mmol), HOBt (351 mg, 2.6 mmol), 2-(3,5-dichlorophenylamino)acetic acid (475 mg, 2.16 mmol) and DIEA (0.574 ml, 3.24 mmol) at 0° C. The solution was stirred at rt over night, diluted with EtOAc (25 mL) and washed with water. The aqueous layer was extracted with EtOAc, 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 (0.4 g, 30%). LCMS [M+1]: 617.

Workup

  1. washwashed with water
  2. extractionThe aqueous layer was extracted with EtOAc
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customto give a residue which
  6. customwas purified by column chromatography (silica gel, gradient 0-2% methanol in chloroform)

Sources & evidence

ORD record
ord-8599a715adf34f1d9f8b3b3870e6933a
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

Loading…