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

HRID 1853517Notes

Reaction equation

HRID 1853517 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-7913e8bec8fb4a6b8e84ccf30871a2fb
Source dataset
uspto-grants-2015_02
Patent number
US08962635B2

Reaction notes

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