Cyclobutanol → Cyclobutyl {4,6-diamino-2-[6-fluoro-3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]pyrimidin-5-yl}carbamate

HRID 626617Notes

Reaction equation

HRID 626617 reaction equation
[CH:1]1([OH:5])[CH2:4][CH2:3][CH2:2]1.ClC(O[C:11](=[O:17])OC(Cl)(Cl)Cl)(Cl)Cl.[F:18][C:19]1[CH:20]=[C:21]2[N:27]([C:28]3[N:33]=[C:32]([NH2:34])[C:31]([NH2:35])=[C:30]([NH2:36])[N:29]=3)[N:26]=[C:25]([CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[F:44])[C:22]2=[N:23][CH:24]=1.C(=O)(O)[O-].[Na+]>ClCCl.N1C=CC=CC=1>[NH2:36][C:30]1[C:31]([NH:35][C:11](=[O:17])[O:5][CH:1]2[CH2:4][CH2:3][CH2:2]2)=[C:32]([NH2:34])[N:33]=[C:28]([N:27]2[C:21]3[C:22](=[N:23][CH:24]=[C:19]([F:18])[CH:20]=3)[C:25]([CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[F:44])=[N:26]2)[N:29]=1

Participants

7

Reactant 4

HCID 76218CyclobutanolHCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 675168882-[6-Fluoro-3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]pyrimidine-4,5,6-triamine

Product 1

HCID 57335162Cyclobutyl {4,6-diamino-2-[6-fluoro-3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]pyrimidin-5-yl}carbamate

Reagents, catalysts & solvents 2

HCID 1049PyridineSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Under argon, 64 ml (0.81 mmol) of cyclobutyl alcohol were initially charged in dichloromethane (4.1 ml), 161 mg (0.54 mmol) of bis(trichloromethyl)carbonate were then added and the mixture was cooled to 0° C. 53 μl (0.65 mmol) of pyridine were then added dropwise, and the reaction mixture was stirred at 0° C. for another 30 min. 200 mg (0.54 mmol) of the compound from example 6A were then added, and the mixture was diluted with 1.4 ml of pyridine. The reaction mixture was stirred at RT overnight, saturated aqueous sodium bicarbonate solution was then added and the mixture was extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and concentrated. The residue was purified by means of preparative RP-HPLC (acetonitrile:water (+0.1% formic acid)−gradient) and the product fractions were concentrated.

Workup

  1. stirringThe reaction mixture was stirred at RT overnight
  2. extractionthe mixture was extracted twice with ethyl acetate
  3. dry with materialThe combined organic phases were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by means of preparative RP-HPLC (acetonitrile:water (+0.1% formic acid)−gradient)
  7. concentrationthe product fractions were concentrated

Sources & evidence

ORD record
ord-dc931a180c9b472da37bd63639b63231
Source dataset
uspto-grants-2016_04
Patent number
US09309239B2

Reaction notes

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