Thionyl Chloride → N-(5-Cyanopyrimidin-4-yl)-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxamide

HRID 510047Notes

Reaction equation

HRID 510047 reaction equation
[F:1][C:2]1[CH:20]=[CH:19][CH:18]=[CH:17][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]([OH:16])=O)=[N:6]1.S(Cl)(Cl)=O.[NH2:25][C:26]1[C:31]([C:32]#[N:33])=[CH:30][N:29]=[CH:28][N:27]=1>N1C=CC=CC=1>[C:32]([C:31]1[C:26]([NH:25][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:17]=[CH:18][CH:19]=[CH:20][C:2]=3[F:1])[N:6]=2)=[O:16])=[N:27][CH:28]=[N:29][CH:30]=1)#[N:33]

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 7372084-Amino-5-pyrimidinecarbonitrileHCID 120182171-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxylic acid

Product 1

HCID 66614381N-(5-Cyanopyrimidin-4-yl)-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

At RT, 39.4 g (145 mmol) of 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxylic acid (preparation described in US2010/004235, page 27) were initially charged, and then thionyl chloride (370 ml) was added. The suspension was heated to reflux for 2 h and the now clear solution was concentrated under reduced pressure. 100 mg (0.345 mmol) of the acid chloride thus prepared were initially charged in pyridine (1.0 ml) and then 41.5 mg (0.345 mmol) of 4-amino-5-cyanopyrimidine were added in portions. The mixture was stirred at RT for 7 h and then left to stand overnight. Subsequently, volatile constituents were removed under high vacuum, 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 30 mg (23% of theory) of the title compound in solid form.

Workup

  1. additionwere initially charged
  2. temperatureThe suspension was heated
  3. temperatureto reflux for 2 h
  4. concentrationthe now clear solution was concentrated under reduced pressure
  5. waitleft
  6. waitto stand overnight
  7. customSubsequently, volatile constituents were removed under high vacuum
  8. customthe residue was separated by means of preparative HPLC (eluent: acetonitrile/water with 0.1% formic acid gradient)
  9. concentrationthe product fractions were concentrated

Sources & evidence

ORD record
ord-f5c09b4e793a4472927890e5d1762a52
Source dataset
uspto-grants-2015_08
Patent number
US09096592B2

Reaction notes

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