Hydrochloric Acid → (2S,6R,8aR)-2-amino-6-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)hexahydroindolizin-3(5H)-one

HRID 919634Notes

Reaction equation

HRID 919634 reaction equation
[O:1]=[C:2]1[N:10]2[C@H:5]([CH2:6][CH2:7][C@@H:8]([NH:11][C:12]3[C:13]4[CH:20]=[CH:19][N:18]([S:21]([C:24]5[CH:30]=[CH:29][C:27]([CH3:28])=[CH:26][CH:25]=5)(=[O:23])=[O:22])[C:14]=4[N:15]=[CH:16][N:17]=3)[CH2:9]2)[CH2:4][C@@H:3]1[NH:31]C(=O)OC(C)(C)C.Cl>CO.O1CCOCC1>[NH2:31][C@@H:3]1[C:2](=[O:1])[N:10]2[C@H:5]([CH2:6][CH2:7][C@@H:8]([NH:11][C:12]3[C:13]4[CH:20]=[CH:19][N:18]([S:21]([C:24]5[CH:25]=[CH:26][C:27]([CH3:28])=[CH:29][CH:30]=5)(=[O:23])=[O:22])[C:14]=4[N:15]=[CH:16][N:17]=3)[CH2:9]2)[CH2:4]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 68070554tert-butyl (2S,6R,8aR)-3-oxo-6-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-octahydroindolizin-2-ylcarbamate

Product 1

HCID 68070553(2S,6R,8aR)-2-amino-6-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)hexahydroindolizin-3(5H)-one

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of tert-butyl (2S,6R,8aR)-3-oxo-6-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-octahydroindolizin-2-ylcarbamate 127.4 (550 mg (1.02 mmole) in MeOH (21 mL) was treated with of 4 M HCl in 1,4-dioxane (4.0 mL (20.3 mmol) and stirred at room temperature for 23 hr. The mixture was concentrated to dryness, and the residue was dissolved in MeOH (20 ml) and treated with polymer-supported carbonate resin (1.2 g, 3.5 mmol/g). The suspension was stirred at room temperature for 1 hour. The resin was removed by filtration through a celite plug, and the filtrate was concentrated in vacuo to yield 414 mg of (2S,6R,8aR)-2-amino-6-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)hexahydroindolizin-3(5H)-one 127.5 as pale yellow solid that was used without further purification. 1H NMR (400 MHz, CHLOROFORM-d) δ 8.42 (s, 1H), 8.04 (d, J=8.3 Hz, 2H), 7.43 (d, J=4.0 Hz, 1H), 7.28 (d, J=8.8 Hz, 2H), 6.49 (d, J=3.8 Hz, 1H), 5.64-5.46 (m, 1H), 4.41 (br. s., 1H), 4.22 (d, J=14.1 Hz, 1H), 3.72-3.54 (m, 2H), 3.08 (dd, J=3.1, 13.9 Hz, 1H), 2.38 (s, 3H), 2.10 (ddd, 0.1=4.3, 8.7, 13.3 Hz, 1H), 2.04-1.91 (m, 1H), 1.90-1.61 (m, 4H), 1.47 (dd, J=2.9, 11.9 Hz, 1H); LCMS (ESI) m/z: 441.2 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated to dryness
  2. dissolutionthe residue was dissolved in MeOH (20 ml)
  3. additiontreated with polymer-supported carbonate resin (1.2 g, 3.5 mmol/g)
  4. stirringThe suspension was stirred at room temperature for 1 hour
  5. customThe resin was removed by filtration through a celite plug
  6. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-09927fd486d24a39ac34a01efc1ab90c
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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