Water → HCID 86706444, compound

HRID 919565Notes

Reaction equation

HRID 919565 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]([CH3:39])[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.O.C([O-])([O-])=O.[K+].[K+]>CO.CCOC(C)=O>[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]([CH3:39])[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 962WaterHCID 11430Potassium CarbonateHCID 86706442HCID 86706442, compound

Product 1

HCID 86706444HCID 86706444, compoundYield 101.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (R)-2-(3,5-dichlorophenylamino)-1-(3-(methyl(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)ethanone (150 mg, 0.25 mmol) in MeOH:H2O (4:1 mL) was added K2CO3 (141 mg, 1.0 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 and the filtrate was then 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 (110 mg, 50%). 1H NMR (400 MHz, DMSO-d6): δ 11.65 (d, J=11.2 Hz, 1H), 8.10 (d, J=6.4 Hz, 1H), 7.14 (d, J=13.6 Hz, 1H), 6.75 (s, 1H), 6.69 (s, 1H), 6.62 (s, 1H), 6.55 (s, 1H), 6.35 (m, 1H), 4.69 (m, 1H), 4.41 (m, 1H), 3.99 (m, 2H), 3.00 (m, 1H), 2.88 (m, 1H), 2.60 (m, 1H), 2.49 (s, 3H), 1.94-1.80 (m, 2H), 1.65 (m, 1H), 1.49 (m, 1H). LC-MS: m/z [M+1]=455.

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 then 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-e8fdcb8636894db6bab3f86fe2891f56
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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