Methyl chloroformate → Methyl {4-amino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6-methylpyrimidin-5-yl}carbamate formate

HRID 510056Notes

Reaction equation

HRID 510056 reaction equation
[F:1][C:2]1[CH:26]=[CH:25][CH:24]=[CH:23][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[N:19]=[C:18]([NH2:20])[C:17]([NH2:21])=[C:16]([CH3:22])[N:15]=2)=[N:6]1.Cl[C:28]([O:30][CH3:31])=[O:29]>N1C=CC=CC=1.ClCCl>[CH:28]([OH:30])=[O:29].[NH2:20][C:18]1[C:17]([NH:21][C:28](=[O:29])[O:30][CH3:31])=[C:16]([CH3:22])[N:15]=[C:14]([C:7]2[C:8]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[N:5]([CH2:4][C:3]3[CH:23]=[CH:24][CH:25]=[CH:26][C:2]=3[F:1])[N:6]=2)[N:19]=1

Participants

5

Reactant 2

HCID 6586Methyl chloroformate3×HCID 582869932-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6-methylpyrimidine-4,5-diamine

Product 1

HCID 86720046Methyl {4-amino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6-methylpyrimidin-5-yl}carbamate formate

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

150 mg (0.343 mmol) of the compound from example 54A were initially charged in pyridine (3 ml) under argon and cooled to 0° C. Subsequently, a solution of 27 μl (0.34 mmol) of methyl chloroformate in dichloromethane (1 ml) was added dropwise, and the mixture was brought to RT and stirred overnight. Then the mixture was cooled again to 0° C., then 5 μl of methyl chloroformate (dissolved in 0.5 ml of dichloromethane) were added and the mixture was stirred at RT for a further 30 min. Subsequently, another 5 μl of methyl chloroformate (dissolved in 0.5 ml of dichloromethane) were added at 0° C. and the mixture was stirred at RT overnight. The reaction mixture was brought to RT and concentrated by rotary evaporation. The residue was separated by means of preparative HPLC (eluent: acetonitrile-water with 0.1% formic acid gradient) and the product fractions were concentrated. This gave 113 mg (71% of theory) of the title compound in solid form.

Workup

  1. customwas brought to RT
  2. temperatureThen the mixture was cooled again to 0° C.
  3. stirringthe mixture was stirred at RT for a further 30 min
  4. stirringthe mixture was stirred at RT overnight
  5. customwas brought to RT
  6. concentrationconcentrated by rotary evaporation
  7. customThe residue was separated by means of preparative HPLC (eluent: acetonitrile-water with 0.1% formic acid gradient)
  8. concentrationthe product fractions were concentrated

Sources & evidence

ORD record
ord-431671aecd7040cbbc61924bd07f2819
Source dataset
uspto-grants-2015_08
Patent number
US09096592B2

Reaction notes

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