Water → 7-((3aS,4R,6R,6aR)-6-(aminomethyl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-N-(2,4-dimethoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

HRID 511600Notes

Reaction equation

HRID 511600 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[C:19]3[N:20]=[CH:21][N:22]=[C:23]([NH:24][CH2:25][C:26]4[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][C:27]=4[O:34][CH3:35])[C:18]=3[CH:17]=[CH:16]2)[CH2:6]1)=[N+]=[N-].C1COCC1.CP(C)C.O>C(Cl)Cl>[NH2:1][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[C:19]3[N:20]=[CH:21][N:22]=[C:23]([NH:24][CH2:25][C:26]4[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][C:27]=4[O:34][CH3:35])[C:18]=3[CH:17]=[CH:16]2)[CH2:6]1

Participants

6

Reactant 4

HCID 962WaterHCID 8028Tetrahydrofuran2×HCID 68983TrimethylphosphineHCID 866661137-((3aS,4R,6R,6aR)-6-(azidomethyl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-N-(2,4-dimethoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Product 1

HCID 677749937-((3aS,4R,6R,6aR)-6-(aminomethyl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-N-(2,4-dimethoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amineYield 93.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 7-((3aS,4R,6R,6aR)-6-(azidomethyl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-N-(2,4-dimethoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (2.23 g, 4.65 mmol) in THF (33 mL, 410 mmol) was cooled to 0° C. and treated dropwise with a 1.0 M solution of trimethylphosphine in THF (9.3 mL, 9.3 mmol). The cold bath was removed and the reaction mixture was allowed to warn to RT with stirring for 1 h; no starting material remained by HPLC. At 1.5 h, water (4.3 mL, 240 mmol) was added and the reaction mixture was stirred for 1 h 15 min; TLC indicated one product. The reaction mixture was concentrated in vacuo to afford a light orange paste. The residue was diluted with CH2Cl2 (120 mL) and washed with water (2×40 mL) and brine (1×40 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo to afford an orange oil. Purification by column chromatography (2×22 cm silica; 0-5% 7 N NH3 in CH3OH/CH2Cl2) afforded the title compound (1.97 g, 53% over 3 steps) as a colorless foam: MS (ESI+) for C24H31N5O4 m/z 454.3 (M+H)+; HPLC purity >95% (ret. time, 2.541 min).

Workup

  1. customThe cold bath was removed
  2. customto warn to RT
  3. waitAt 1.5 h
  4. stirringthe reaction mixture was stirred for 1 h 15 min
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. customto afford a light orange paste
  7. washwashed with water (2×40 mL) and brine (1×40 mL)
  8. dry with materialThe organic layer was dried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customto afford an orange oil
  11. customPurification by column chromatography (2×22 cm silica; 0-5% 7 N NH3 in CH3OH/CH2Cl2)

Sources & evidence

ORD record
ord-552ff7b75ad24ec0883a8e45dccbb4ca
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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