Water → HCID 67516775, compound

HRID 919619Notes

Reaction equation

HRID 919619 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][CH2:10][C:11]([N:13]2[CH2:18][CH2:17][CH:16]([CH3:19])[CH:15]([NH:20][C:21]3[C:22]4[CH:29]=[CH:28][N:27](S(C5C=CC(C)=CC=5)(=O)=O)[C:23]=4[N:24]=[CH:25][N:26]=3)[CH2:14]2)=[O:12])[CH:5]=[C:6]([Cl:8])[CH:7]=1.O.C([O-])([O-])=O.[K+].[K+]>CO.CCOC(C)=O>[N:24]1[C:23]2[NH:27][CH:28]=[CH:29][C:22]=2[C:21]([NH:20][CH:15]2[CH:16]([CH3:19])[CH2:17][CH2:18][N:13]([C:11](=[O:12])[CH2:10][NH:9][C:4]3[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[CH:3]=3)[CH2:14]2)=[N:26][CH:25]=1

Participants

6

Reactant 3

HCID 962WaterHCID 11430Potassium CarbonateHCID 86706478HCID 86706478, compound

Product 1

HCID 67516775HCID 67516775, compoundYield 27.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-(3,5-dichlorophenylamino)-1-(4-methyl-3-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl)ethanone (100 mg, 0.17 mmol) in MeOH:H2O (4:1 mL) was added K2CO3 (94 mg, 0.68 mmol) and the reaction mixture was heated to 60° C. for 1 h. The reaction mixture was concentrated in vacuo and the residue obtained was diluted in EtOAc (50 mL). The EtOAc suspension was filtered through celite, the filtrate was dried over Na2SO4, and concentrated in vacuo to give a residue that was subjected to purification by column chromatography (silica gel, gradient MeOH in DCM) to afford the titled intermediate (20 mg, 27%). 1H NMR (400 MHz, DMSO-d6): δ 11.61-11.45 (m, 1H), 8.19-8.06 (m, 1H), 7.08-6.43 (m, 5H), 6.22-6.15 (m, 1H), 4.59-4.21 (m, 2H), 4.15-3.75 (m, 3H), 3.25-2.98 (m, 2H), 2.78-2.45 (m, 1H), 2.15-1.99 (m, 1H), 1.86-1.7-62 (m, 2H), 0.98-0.77 (m, 3H). LC-MS: m/z [M+1]=433.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue obtained
  3. filtrationThe EtOAc suspension was filtered through celite
  4. dry with materialthe filtrate was dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customto give a residue that
  7. customwas subjected to purification by column chromatography (silica gel, gradient MeOH in DCM)

Sources & evidence

ORD record
ord-5e7f282a1b924f9bb8b0cc62d0df86e4
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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