Triphenylphosphine → tert-butyl (2R)-2-([4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)pyrrolidine-1-carboxylate

HRID 1529869Notes

Reaction equation

HRID 1529869 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[CH2:13][C@H:14]1[CH2:18][CH2:17][CH2:16][N:15]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O.CN(C)C=O>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([CH2:13][C@H:14]3[CH2:18][CH2:17][CH2:16][N:15]3[C:19]([O:21][C:22]([CH3:23])([CH3:25])[CH3:24])=[O:20])[N:3]=[C:2]([I:1])[C:10]=12

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 688279N-(tert-Butoxycarbonyl)-D-prolinolHCID 5363146Diisopropyl azodicarboxylateHCID 178508725HCID 178508725, compound

Product 1

HCID 86714463tert-butyl (2R)-2-([4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)pyrrolidine-1-carboxylateYield 7.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

Into a 1 L, 2-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (10 g, 38.31 mmol, 1.00 equiv), tert-butyl (2R)-2-(hydroxymethyl)pyrrolidine-1-carboxylate (15.4 g, 76.52 mmol, 2.00 equiv), PPh3 (20.1 g, 76.63 mmol, 2.00 equiv), and N,N-dimethylformamide (400 mL). DIAD (15.5 g, 76.65 mmol, 2.00 equiv) was added dropwise over 30 min. The resulting solution was stirred for 12 h at 25° C. and then diluted with 1 L of water. The resulting solution was extracted with ethyl acetate and the organic layers combined and washed with brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum and the residue was placed on a silica gel column and eluted with chloroform/methanol (100/1) to give 1.2 g (6%) of tert-butyl (2R)-2-([4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)pyrrolidine-1-carboxylate as a off-white solid.

Workup

  1. customInto a 1 L, 2-necked round-bottom flask purged
  2. temperaturemaintained under an inert atmosphere of nitrogen
  3. extractionThe resulting solution was extracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialThe mixture was dried over anhydrous sodium sulfate
  6. concentrationconcentrated under vacuum
  7. washeluted with chloroform/methanol (100/1)

Sources & evidence

ORD record
ord-de4f2a61b5a246bc9ca176b65c242689
Source dataset
uspto-grants-2015_07
Patent number
US09090621B2

Reaction notes

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