Diisopropylethylamine → HCID 178527017, compound

HRID 1241340Notes

Reaction equation

HRID 1241340 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([P:12](=[O:15])([OH:14])[OH:13])([OH:11])[PH2:9]=[O:10])=[CH:4][CH:3]=1.C([Si](C)(C)[O:21][C:22]1[CH:23]=[C:24]([CH2:28][CH2:29][N:30]2[CH:38]=[N:37][C:36]3[C:31]2=[N:32][C:33]([F:40])=[N:34][C:35]=3Cl)[CH:25]=[CH:26][CH:27]=1)(C)(C)C.C(N(CC)C(C)C)(C)C>CS(C)=O>[F:40][C:33]1[N:32]=[C:31]2[C:36]([N:37]=[CH:38][N:30]2[CH2:29][CH2:28][C:24]2[CH:25]=[CH:26][CH:27]=[C:22]([OH:21])[CH:23]=2)=[C:35]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]([P:12](=[O:13])([OH:14])[OH:15])([OH:11])[PH2:9]=[O:10])=[CH:6][CH:7]=2)[N:34]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 219337779-{2-[3-(tert-Butyl-dimethyl-silanyloxy)-phenyl]ethyl}-6-chloro-2-fluoro-9H-purineHCID 178507648HCID 178507648, compound

Product 1

HCID 178527017HCID 178527017, compoundYield 58.7%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A sealed pressure flask, flushed with N2, containing a mixture of crude [(4-Amino-phenyl)-hydroxy-phosphinoylmethyl]-phosphonic acid (8.29 mmol), 9-{2-[3-(tert-Butyl-dimethyl-silanyloxy)-phenyl]-ethyl}-6-chloro-2-fluoro-9H-purine (3.37 g, 8.29 mmol), and N,N-diisopropylethylamine (7.2 mL, 41.5 mmol) in 45.0 mL DMSO was heated at 110–120° C. for 13 h. Upon removing excess N,N-diisopropylethylamine (N2 flow, slight heat) the slightly brown solution was cooled to ambient temperature and added ˜500 mL of H2O to produce a milky, off-white solution. Further precipitation occurred upon addition of TFA (final pH=1–2), at which time the mixture was heated (100° C. hot plate) and stirred vigorously for ˜20 min, filtered while hot, then washed with acidified H2O (TFA, pH=1–2; 4×20 mL), EtOH (2×20 mL), and Et2O (4×20 mL). Isolation of a second crop from the concentrated filtrate in the same manner as described above, followed by removal of excess solvent (in vacuo) provided 2.47 g of an off-white solid: m/z 506 (M−H).

Workup

  1. customA sealed pressure flask, flushed with N2
  2. additioncontaining
  3. temperaturewas heated at 110–120° C. for 13 h
  4. customUpon removing excess N,N-diisopropylethylamine (N2 flow, slight heat) the slightly brown solution
  5. additionadded ˜500 mL of H2O
  6. customto produce a milky, off-white solution
  7. customFurther precipitation
  8. additionoccurred upon addition of TFA (final pH=1–2), at which time the mixture
  9. temperaturewas heated (100° C. hot plate)
  10. filtrationfiltered while hot,
  11. washthen washed with acidified H2O (TFA, pH=1–2; 4×20 mL), EtOH (2×20 mL), and Et2O (4×20 mL)
  12. customfollowed by removal of excess solvent (in vacuo)

Sources & evidence

ORD record
ord-4544490734ca4418a445455503f2e003
Source dataset
uspto-grants-2006_10
Patent number
US07115589B2

Reaction notes

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