Hydrochloric Acid → 3-iodo-1-tetrahydro-1H-3-pyrrolyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine hydrochloride

HRID 897930Notes

Reaction equation

HRID 897930 reaction equation
[I:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[NH:4][N:3]=1.O[CH:13]1[CH2:17][CH2:16][N:15](C(OC(C)(C)C)=O)[CH2:14]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.[ClH:56]>O1CCCC1.CC(C)=O>[ClH:56].[I:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([CH:13]2[CH2:17][CH2:16][NH:15][CH2:14]2)[N:3]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 44169391-Boc-3-pyrrolidinolHCID 178508725HCID 178508725, compound

Product 1

HCID 223473313-iodo-1-tetrahydro-1H-3-pyrrolyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine hydrochlorideYield 65%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (5.610 g, 21.49 mmol) in tetrahydrofuran (200 mL) was added rac-tert-butyl 3-hydroxy-1-pyrrolidinecarboxylate (6.039 g, 32.25 mmol), triphenylphosphine (11.273 g, 42.98 mmol), and diethyl azodicarboxylate (7.485 g, 6.77 mL, 42.98 mmol). The reaction mixture was stirred at room temperature for 6 days and then concentrated to afford an orange-brown oil. Acetone (100 mL) and 5 N hydrochloric acid (50 mL) were added and the solution was heated at 40° C. for 18 h and then cooled to room temperature. The resulting yellow precipitate was filtered, and the filter cake was washed with diethyl ether and dried to afford rac-3-iodo-1-tetrahydro-1H-3-pyrrolyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine monohydrochloride as an off-white solid (5.153 g, 65%). RP-HPLC Rt 4.079 min, 99% purity (5% to 85% acetonitrile/0.1M aqueous ammonium acetate, buffered to pH 4.5, over 20 min at 1 mL/min; λ=254 nm; Deltapak C18, 300 Å, 5 μm, 150×3.9 mm column); m/z 331 (MH+).

Workup

  1. concentrationconcentrated
  2. customto afford an orange-brown oil
  3. temperaturethe solution was heated at 40° C. for 18 h
  4. temperaturecooled to room temperature
  5. filtrationThe resulting yellow precipitate was filtered
  6. washthe filter cake was washed with diethyl ether
  7. customdried

Sources & evidence

ORD record
ord-36f699182e524f4f80c067db86a43837
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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