Water → 9-((3aS,4R,6R,6aR)-6-(aminomethyl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-N-(2,4-dimethoxybenzyl)-9H-purin-6-amine

HRID 511572Notes

Reaction equation

HRID 511572 reaction equation
[N:1]([CH2:4][C@@H:5]1[C@H:9]2[O:10][C:11]([CH3:14])([CH3:13])[O:12][C@H:8]2[C@H:7]([N:15]2[CH:23]=[N:22][C:21]3[C:16]2=[N:17][CH:18]=[N:19][C:20]=3[NH:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][C:27]=2[O:34][CH3:35])[CH2:6]1)=[N+]=[N-].CP(C)C.O>C1COCC1.C(Cl)Cl>[NH2:1][CH2:4][C@@H:5]1[C@H:9]2[O:10][C:11]([CH3:13])([CH3:14])[O:12][C@H:8]2[C@H:7]([N:15]2[CH:23]=[N:22][C:21]3[C:16]2=[N:17][CH:18]=[N:19][C:20]=3[NH:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][C:27]=2[O:34][CH3:35])[CH2:6]1

Participants

6

Reactant 3

HCID 962WaterHCID 68983TrimethylphosphineHCID 866661049-((3aS,4R,6R,6aR)-6-(azidomethyl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-N-(2,4-dimethoxybenzyl)-9H-purin-6-amine

Product 1

HCID 677765029-((3aS,4R,6R,6aR)-6-(aminomethyl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-N-(2,4-dimethoxybenzyl)-9H-purin-6-amineYield 98.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 9-((3aS,4R,6R,6aR)-6-(azidomethyl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-N-(2,4-dimethoxybenzyl)-9H-purin-6-amine (1.72 g, 3.58 mmol) in THF (16 mL) was cooled to 0° C. (ice/brine bath) and treated dropwise with a 1.0 M solution of trimethylphosphine in THF (6.30 mL, 6.30 mmol). The cold bath was removed after 30 min and the reaction mixture was stirred for 1.5 h; HPLC/LC MS indicated complete consumption of the starting azide. Water (2.84 mL, 157 mmol) was added to the orange solution (gas evolution noted) and the reaction mixture was stirred for 2.75 h at rt; HPLC indicated complete conversion to the desired amine. The reaction mixture was concentrated in vacuo to afford an orange oil. The residue was taken up in CH2Cl2 (150 mL) and washed with water (2×50 mL) and brine (1×75 mL). The separated organic layer was dried (Na2SO4) and concentrated in vacuo to afford the title compound (1.6 g, 98%) as a pale yellow foam: MS (ESI+) for C23H30N6O4 m/z 455.2 (M+H)+.

Workup

  1. customThe cold bath was removed after 30 min
  2. customconsumption of the starting azide
  3. stirringthe reaction mixture was stirred for 2.75 h at rt
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. customto afford an orange oil
  6. washwashed with water (2×50 mL) and brine (1×75 mL)
  7. dry with materialThe separated organic layer was dried (Na2SO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d7263f4b937f40b092b93b2d9be42bae
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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