Diisopropylethylamine → tert-butyl (2S,6R,8aR)-3-oxo-6-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-octahydroindolizin-2-ylcarbamate

HRID 919633Notes

Reaction equation

HRID 919633 reaction equation
[NH2:1][CH:2]1[CH2:10][CH2:9][CH:8]2[N:4]([C:5](=[O:19])[C@@H:6]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:7]2)[CH2:3]1.Cl[C:21]1[C:22]2[CH:29]=[CH:28][N:27]([S:30]([C:33]3[CH:39]=[CH:38][C:36]([CH3:37])=[CH:35][CH:34]=3)(=[O:32])=[O:31])[C:23]=2[N:24]=[CH:25][N:26]=1.CCN(C(C)C)C(C)C>CN(C=O)C.O>[O:19]=[C:5]1[N:4]2[C@@H:8]([CH2:9][CH2:10][C@H:2]([NH:1][C:21]3[C:22]4[CH:29]=[CH:28][N:27]([S:30]([C:33]5[CH:39]=[CH:38][C:36]([CH3:37])=[CH:35][CH:34]=5)(=[O:31])=[O:32])[C:23]=4[N:24]=[CH:25][N:26]=3)[CH2:3]2)[CH2:7][C@@H:6]1[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:15])([CH3:16])[CH3:17].[O:19]=[C:5]1[N:4]2[C@H:8]([CH2:9][CH2:10][C@@H:2]([NH:1][C:21]3[C:22]4[CH:29]=[CH:28][N:27]([S:30]([C:33]5[CH:39]=[CH:38][C:36]([CH3:37])=[CH:35][CH:34]=5)(=[O:31])=[O:32])[C:23]=4[N:24]=[CH:25][N:26]=3)[CH2:3]2)[CH2:7][C@@H:6]1[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:15])([CH3:16])[CH3:17]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 442289674-Chloro-7-(p-toluenesulfonyl)-7H-pyrrolo[2,3-d]pyrimidineHCID 68070552tert-butyl(2S)-6-amino-3-oxooctahydroindolizin-2-ylcarbamate

Product 2

HCID 68070554tert-butyl (2S,6R,8aR)-3-oxo-6-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-octahydroindolizin-2-ylcarbamateHCID 68070555tert-butyl (2S,6S,8aS)-3-oxo-6-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)octahydroindolizin-2-ylcarbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of tert-butyl(2S)-6-amino-3-oxooctahydroindolizin-2-ylcarbamate 127.2 (0.913 g, 3.39 mmol) in DMF (25 ml) and was added 4-chloro-7-tosyl-7H-pyrrolo[2,3-d]pyrimidine (100 mg (3.4 mmole) 127.a and DIEA (1.18 mL (6.78 mmole) at solution was heated 90° C. for 24 hr. After cooling to room temperature, the mixture was diluted with H2O and washed with EtOAc (2×). The combined organics were washed with H2O and brine, dried over MgSO4, filtered, and concentrated in vacuo, absorbing onto 6 g silica gel. Purification by flash column chromatography (ISCO 40 g SiO2, 50% EtOAc/hexanes then gradient to 100% EtOAc/hexanes) yielded 0.52 g of tert-butyl (2S,6S,8aS)-3-oxo-6-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)octahydroindolizin-2-ylcarbamate 127.3 and 0.55 g of tert-butyl (2S,6R,8 aR)-3-oxo-6-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)octahydroindolizin-2-ylcarbamate 127.4.

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with EtOAc (2×)
  3. washThe combined organics were washed with H2O and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customabsorbing onto 6 g silica gel
  8. customPurification by flash column chromatography (ISCO 40 g SiO2, 50% EtOAc/hexanes

Sources & evidence

ORD record
ord-40617adba984408291a22ea538ed4848
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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