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

HRID 919583Notes

Reaction equation

HRID 919583 reaction equation
[CH2:1]([N:3]([C@H:23]1[CH2:28][CH2:27][CH2:26][NH:25][CH2:24]1)[C:4]1[C:5]2[CH:12]=[CH:11][N:10]([S:13]([C:16]3[CH:22]=[CH:21][C:19]([CH3:20])=[CH:18][CH:17]=3)(=[O:15])=[O:14])[C:6]=2[N:7]=[CH:8][N:9]=1)[CH3:2].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[Cl:50][C:51]1[CH:52]=[C:53]([NH:58][CH2:59][C:60](O)=[O:61])[CH:54]=[C:55]([Cl:57])[CH:56]=1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[Cl:50][C:51]1[CH:52]=[C:53]([NH:58][CH2:59][C:60]([N:25]2[CH2:26][CH2:27][CH2:28][C@H:23]([N:3]([CH2:1][CH3:2])[C:4]3[C:5]4[CH:12]=[CH:11][N:10]([S:13]([C:16]5[CH:22]=[CH:21][C:19]([CH3:20])=[CH:18][CH:17]=5)(=[O:14])=[O:15])[C:6]=4[N:7]=[CH:8][N:9]=3)[CH2:24]2)=[O:61])[CH:54]=[C:55]([Cl:57])[CH:56]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 13138167(3,5-Dichlorophenyl)glycineHCID 118906729(S)-N-ethyl-N-(piperidin-3-yl)-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Product 1

HCID 86706457(S)-2-(3,5-dichlorophenylamino)-1-(3-(ethyl(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)ethanoneYield 83.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)—N-ethyl-N-(piperidin-3-yl)-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (60 mg, 0.15 mmol), in DMF (5 mL), was added EDCI (34 mg, 0.18 mmol), HOBt (24 mg, 0.18 mmol), 2-(3,5-dichlorophenylamino)acetic acid (33 mg, 0.15 mmol) and DIEA (0.06 mL, 0.36 mmol) at 0° C. The reaction mixture was stirred overnight at rt. After completion of the reaction, the reaction mixture was diluted with EtOAc (25 mL) and the organic phase was washed with water (10 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo to give the crude compound that was purified by column chromatography (silica gel, gradient MeOH in CH2Cl2) to afford the titled compound (75 mg, 82%). LC-MS: m/z [M+1]=601.

Workup

  1. customAfter completion of the reaction
  2. washthe organic phase was washed with water (10 mL)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customto give the crude compound that
  6. customwas purified by column chromatography (silica gel, gradient MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-3b97322cd3ae419883c11ee7d8844959
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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