Potassium Carbonate → (2S,6R,8aR)-6-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-2-(3-chloro-5-fluorophenylamino)hexahydroindolizin-3(5H)-one

HRID 919636Notes

Reaction equation

HRID 919636 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C@@H:10]2[C:18](=[O:19])[N:17]3[C@H:12]([CH2:13][CH2:14][C@@H:15]([NH:20][C:21]4[C:22]5[CH:29]=[CH:28][N:27](S(C6C=CC(C)=CC=6)(=O)=O)[C:23]=5[N:24]=[CH:25][N:26]=4)[CH2:16]3)[CH2:11]2)[CH:5]=[C:6]([F:8])[CH:7]=1.C([O-])([O-])=O.[K+].[K+]>CO.O>[N:24]1[C:23]2[NH:27][CH:28]=[CH:29][C:22]=2[C:21]([NH:20][C@@H:15]2[CH2:14][CH2:13][C@H:12]3[N:17]([C:18](=[O:19])[C@@H:10]([NH:9][C:4]4[CH:5]=[C:6]([F:8])[CH:7]=[C:2]([Cl:1])[CH:3]=4)[CH2:11]3)[CH2:16]2)=[N:26][CH:25]=1

Participants

5

Reactant 2

HCID 11430Potassium CarbonateHCID 68070556(2S,6R,8aR)-2-(3-chloro-5-fluorophenylamino)-6-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)hexahydroindolizin-3(5H)-one

Product 1

HCID 68070557(2S,6R,8aR)-6-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-2-(3-chloro-5-fluorophenylamino)hexahydroindolizin-3(5H)-oneYield 50.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
70 °C

Procedure

A solution of (2S,6R,8aR)-2-(3-chloro-5-fluorophenylamino)-6-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)hexahydroindolizin-3(5H)-one (19 mg) 127.6 in MeOH (0.5 mL) & H2O (2 mL) was treated with of K2CO3 (5 mg, 0.033 mmol) and heated at 70° C. for 24 hours. The white suspension was cooled and diluted with H2O. The precipitate was collected on a Whatman 0.45 um nylon membrane filter and concentrated in vacuo to afford of (2S,6R,8aR)-6-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-2-(3-chloro-5-fluorophenylamino)hexahydroindolizin-3(5H)-one 127.7 (7 mg) as a white solid that exists as 3:1 mixture of diasteromers. LCMS (ESI) m/z: 415.2 [M+H]+.

Workup

  1. temperatureThe white suspension was cooled
  2. customThe precipitate was collected on a Whatman 0.45 um nylon membrane
  3. filtrationfilter
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3fc55ab2bdcc422cb31d43b77f7ecfcf
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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