Ethylene Glycol → HCID 91095343, compound

HRID 1093195Notes

Reaction equation

HRID 1093195 reaction equation
C12OC(CC1)CN(C1N=C(C3C=CC(N)=CC=3)N=C3N(C(COC)COC)N=CC=13)C2.ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.[CH2:44]([OH:47])[CH2:45][OH:46].[CH3:48][O:49][CH2:50][CH:51]([N:55]1[C:59]2=[N:60][C:61]([C:72]3[CH:77]=[CH:76][C:75]([N:78]=[C:79]=[O:80])=[CH:74][CH:73]=3)=[N:62][C:63]([N:64]3[CH2:70][CH:69]4[O:71][CH:66]([CH2:67][CH2:68]4)[CH2:65]3)=[C:58]2[CH:57]=[N:56]1)[CH2:52][O:53][CH3:54]>ClCCl.C(N(CC)CC)C>[OH:46][CH2:45][CH2:44][O:47][C:79](=[O:80])[NH:78][C:75]1[CH:74]=[CH:73][C:72]([C:61]2[N:60]=[C:59]3[N:55]([CH:51]([CH2:50][O:49][CH3:48])[CH2:52][O:53][CH3:54])[N:56]=[CH:57][C:58]3=[C:63]([N:64]3[CH2:65][CH:66]4[O:71][CH:69]([CH2:68][CH2:67]4)[CH2:70]3)[N:62]=2)=[CH:77][CH:76]=1

Participants

7

Reactant 4

HCID 174Ethylene GlycolHCID 94429TriphosgeneHCID 66589060HCID 66589060, compoundHCID 87063257HCID 87063257, compound

Product 1

HCID 91095343HCID 91095343, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

A solution of 4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(1,3-dimethoxypropan-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)aniline (65 mg, 0.15 mmol) in dichloromethane (1.5 mL) was treated with triethylamine (0.2 mL), followed by a solution of triphosgene (23 mg, 0.08 mmol) in dichloromethane (1 mL). After the passage of 10 minutes, the appropriate nucleophile—in the case, ethylene glycol (84 μL, 1.5 mmol)—was added to the 3-(1-(1,3-dimethoxypropan-2-yl)-6-(4-isocyanatophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane (“isocyanate”) mixture. After 3 hours, the reaction mixture was concentrated to dryness under reduced pressure. The residue was purified by reverse-phase high performance liquid chromatography using a Phenomenex Prodigy 21 mm×250 mm column, running a gradient elution of 5% acetonitrile/95% of 0.1% aqueous trifluoroacetic acid to 100% acetonitrile to provide 2-hydroxyethyl(4-{1-[2-methoxy-1-(methoxymethyl)ethyl]-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)carbamate (41 mg, 53%). MS (ES+): 513.2 (M+H)+

Workup

  1. concentrationthe reaction mixture was concentrated to dryness under reduced pressure
  2. customThe residue was purified by reverse-phase high performance liquid chromatography
  3. washa gradient elution of 5% acetonitrile/95% of 0.1% aqueous trifluoroacetic acid to 100% acetonitrile

Sources & evidence

ORD record
ord-b6d46b7ba8dc48d5af3f578954409594
Source dataset
uspto-grants-2012_03
Patent number
US08129371B2

Reaction notes

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