Triphenylphosphine → HCID 22346916, compound

HRID 898035Notes

Reaction equation

HRID 898035 reaction equation
[I:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])N[N:3]=1.O[CH:13]1[CH2:18][CH2:17][CH:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:15][CH2:14]1.[C:24]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1.O>[NH2:11][C:9]1[C:10]2[C:2]([I:1])=[N:3][CH:24]([CH:13]3[CH2:18][CH2:17][CH:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:15][CH2:14]3)[C:5]=2[N:6]=[CH:7][N:8]=1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 86973Ethyl 4-hydroxycyclohexanecarboxylateHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 178508725HCID 178508725, compound

Product 1

HCID 22346916HCID 22346916, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

3-Iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.52 g, 2.0 mmol), ethyl 4-hydroxycyclohexanecarboxylate (0.806 mL, 5.0 mmol, triphenylphosphine (1.05 g, 4.0 mmol), diethyl azodicarboxylate (0.628 mL, 4.0 mmol) were suspended in tetrahydrofuran (15 mL), and the mixture was stirred at ambient temperature under a gentle flow of nitrogen for 48 h. The mixture was diluted with water (50 mL), and extracted with ethyl acetate (3×50 mL). The organic fractions were combined, dried over magnesium sulfate, filtered, and concentrated. The residue was partially purified by flash column chromatography (100% ethyl acetate) to afford ethyl 4-(4-amino-5-iodo-7H-pyrrolo[3,4-d]pyrimidin-7-yl)-1-cyclohexanecarboxylate as a mixture of cis- and trans-diastereomers, along with triphenylphosphine oxide. Repurification of the mixture by flash column chromatography on silica gel deactivated with triethylamine (0.5% methanol/dichloromethane as eluant) afforded the desired cis-ethyl 4-(4-amino-5-iodo-7H-pyrrolo[3,4-d]pyrimidin-7-yl)-1-cyclohexanecarboxylate as a yellow solid (0.260 g, 0.625 mmol): RP-HPLC (25 to 100% acetonitrile in 0.1 M aqueous ammonium acetate over 10 min at 1 mL/min using a 5μ Hypersil HS C18, 250×4.6 mm column) Rt 9.55 min; MS (MH)+ 416.

Workup

  1. extractionextracted with ethyl acetate (3×50 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was partially purified by flash column chromatography (100% ethyl acetate)

Sources & evidence

ORD record
ord-70a9de594cce4836a0d2d4946759bcd8
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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