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

HRID 919584Notes

Reaction equation

HRID 919584 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][CH2:10][C:11]([N:13]2[CH2:18][CH2:17][CH2:16][C@H:15]([N:19]([CH2:39][CH3:40])[C:20]3[C:21]4[CH:28]=[CH:27][N:26](S(C5C=CC(C)=CC=5)(=O)=O)[C:22]=4[N:23]=[CH:24][N:25]=3)[CH2:14]2)=[O:12])[CH:5]=[C:6]([Cl:8])[CH:7]=1.C([O-])([O-])=O.[K+].[K+].CO>CO.O.C(Cl)Cl>[Cl:8][C:6]1[CH:5]=[C:4]([NH:9][CH2:10][C:11]([N:13]2[CH2:18][CH2:17][CH2:16][C@H:15]([N:19]([CH2:39][CH3:40])[C:20]3[C:21]4[CH:28]=[CH:27][NH:26][C:22]=4[N:23]=[CH:24][N:25]=3)[CH2:14]2)=[O:12])[CH:3]=[C:2]([Cl:1])[CH:7]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 11430Potassium CarbonateHCID 86706457(S)-2-(3,5-dichlorophenylamino)-1-(3-(ethyl(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)ethanone

Product 1

HCID 56971627(S)-2-(3,5-dichlorophenylamino)-1-(3-(ethyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)ethanoneYield 50.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22242641Methanol--water (1/1)Solvent

Conditions

Temperature
60 °C

Procedure

To a solution of (S)-2-(3,5-dichlorophenylamino)-1-(3-(ethyl(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl) ethanone (70 mg, 0.11 mmol) in MeOH:H2O (4:1, 10 mL), K2CO3 (48 mg, 0.35 mmol) was added and the reaction mixture was heated at 60° C. for 1 h, the reaction was monitored by TLC. After completion of reaction, the reaction mixture was concentrated under vacuo to give a residue. The residue triturated with 10% MeOH in EtOAc (15 mL), the suspension was filtrated, the filtrate was evaporated under vacuo to give the crude compound that was subjected to column chromatography (silica gel, gradient MeOH in CH2Cl2) to afford (25 mg, 45%) of the titled compound. 1H NMR (400 MHz, DMSO-d6): δ 11.79 and 11.6 (2s, 1H), 8.106 (d, J=6.8 Hz, 1H), 7.18 and 7.13 (2s, 1H), 6.76 (s, 1H), 6.69 (s, 1H), 6.62 (s, 1H), 6.49 and 6.43 (2s, 1H), 6.37 and 6.33 (2t, J=2.3 Hz, 1H), 4.74-4.69 (m, 1H), 4.46-4.39 (m, 1H), 4.13-3.88 (m, 4H), 3.76-3.70 (m, 2H), 3.20-3.16 (m, 1H), 3.00 (t, J=12.0 Hz, 1H), 2.86 (t, J=12.0 Hz, 1H), 2.62 (t, J=13.6 Hz, 1H), 1.98-1.81 (m, 3H), 1.65-1.49 (m, 1H), 1.19 (t, J=6.8 Hz, 3H). LC-MS: m/z [M+1]=447. HPLC (254 nm): 97.68%. HPLC (210 nm): 98.20%.

Workup

  1. customAfter completion of reaction
  2. concentrationthe reaction mixture was concentrated under vacuo
  3. customto give a residue
  4. customThe residue triturated with 10% MeOH in EtOAc (15 mL)
  5. filtrationthe suspension was filtrated
  6. customthe filtrate was evaporated under vacuo
  7. customto give the crude compound that

Sources & evidence

ORD record
ord-a6a7ebae2ccb4252804306d775792757
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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