Ethylene Glycol → HCID 91370646, compound

HRID 1093175Notes

Reaction equation

HRID 1093175 reaction equation
[CH:1]12[O:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][N:3]([C:9]1[N:14]=[C:13]([C:15]3[CH:21]=[CH:20][C:18]([NH2:19])=[CH:17][CH:16]=3)[N:12]=[C:11]3[N:22]([CH:25]4[CH2:30][CH2:29][N:28]([CH2:31][C:32]([F:35])([F:34])[F:33])[CH2:27][CH2:26]4)[N:23]=[CH:24][C:10]=13)[CH2:2]2.ClC(Cl)(O[C:40](=[O:46])[O:41][C:42](Cl)(Cl)Cl)Cl.C(N(CC)CC)C.C(O)[CH2:56][OH:57]>O1CCCC1>[OH:57][CH2:56][CH2:42][O:41][C:40](=[O:46])[NH:19][C:18]1[CH:20]=[CH:21][C:15]([C:13]2[N:12]=[C:11]3[N:22]([CH:25]4[CH2:26][CH2:27][N:28]([CH2:31][C:32]([F:34])([F:35])[F:33])[CH2:29][CH2:30]4)[N:23]=[CH:24][C:10]3=[C:9]([N:3]3[CH2:4][CH:5]4[O:8][CH:1]([CH2:7][CH2:6]4)[CH2:2]3)[N:14]=2)=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 174Ethylene GlycolHCID 8471TriethylamineHCID 94429TriphosgeneHCID 66589022HCID 66589022, compound

Product 1

HCID 91370646HCID 91370646, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)aniline (85 mg, 0.17 mmol) in tetrahydrofuran (6 mL) was treated with triphosgene (26 mg, 0.09 mmol), followed by triethylamine (0.11 mL). After the passage of five minutes, ethylene glycol (0.14 mL) was added. The mixture was concentrated to dryness under reduced pressure. The resultant residue was purified via reverse-phase high performance liquid chromatography using a Phenomenex Gemini 21 mm×100 mm column, running a gradient elution of 10% acetonitrile/90% of 0.1% aqueous trifluoroacetic acid to 70% acetonitrile over 20 minutes. After the concentration of fractions under reduced pressure, 2-hydroxyethyl(4-{4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)carbamate (55 mg, 56%) was obtained as clear blond semi-solid. MS (ES+): 576.1, 577.1 (M+H)+

Workup

  1. concentrationThe mixture was concentrated to dryness under reduced pressure
  2. customThe resultant residue was purified via reverse-phase high performance liquid chromatography
  3. washa gradient elution of 10% acetonitrile/90% of 0.1% aqueous trifluoroacetic acid to 70% acetonitrile over 20 minutes

Sources & evidence

ORD record
ord-4dfb12530ca54b8e881b994144bb7a19
Source dataset
uspto-grants-2012_03
Patent number
US08129371B2

Reaction notes

Loading…