Triethylamine → HCID 10001882, compound

HRID 720258Notes

Reaction equation

HRID 720258 reaction equation
Cl.[F:2][C:3]1[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:4]=1[CH2:5][N:6]1[C:10]2=[N:11][CH:12]=[CH:13][CH:14]=[C:9]2[C:8]([C:15](=[NH:17])[NH2:16])=[N:7]1.C[N:24]([CH:26]=[C:27]1[CH:32]=CN=C(CC#N)[CH2:28]1)C.C([N:38]([CH2:41][CH3:42])[CH2:39][CH3:40])C>C(O)C1C=CC=CC=1.C(O)C(C)C>[F:2][C:3]1[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:4]=1[CH2:5][N:6]1[C:10]2=[N:11][CH:12]=[CH:13][CH:14]=[C:9]2[C:8]([C:15]2[N:16]=[C:26]([NH2:24])[C:27]([C:32]3[CH:40]=[CH:39][N:38]=[CH:41][CH:42]=3)=[CH:28][N:17]=2)=[N:7]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 21891671HCID 21891671, compoundHCID 86586427HCID 86586427, compound2×

Product 1

HCID 10001882HCID 10001882, compound

Reagents, catalysts & solvents 2

HCID 244Benzyl AlcoholSolvent2×HCID 6560IsobutanolSolvent2×

Conditions

Temperature
113 °C

Procedure

680 mg (1.88 mmol) of 1-(2,3-difluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboximidamide hydrochloride from Example 28 A and 358 mg (2.07 mmol) of 4-[(dimethylamino)methylene]pyridineacetonitrile from Example 32 A are suspended in a 3:1 benzyl alcohol:isobutanol mixture at RT. Then 38.1 mg (0.38 mmol) of triethylamine are added, and the mixture is stirred at 87–90° C. overnight. A further 0.5 eq. of 4-[(dimethylamino)methylene]pyridineacetonitrile from Example 32 A is added, and the mixture is stirred at 87–90° C. for a further 6 hours. It is diluted with 3 ml of benzyl alcohol and 19 ml of isobutanol and briefly heated at 113° C. It is filtered hot, and the filtrate is slowly cooled while stirring. The solvent is then removed in vacuo, and the product is absorbed on silica gel. It is chromatographed (mobile phase: dichloromethane:methanol 30:1-20:1). The combined pure fractions are recombined and purified by preparative RP-HPLC.

Workup

  1. customat RT
  2. stirringthe mixture is stirred at 87–90° C. for a further 6 hours
  3. filtrationIt is filtered hot
  4. temperaturethe filtrate is slowly cooled
  5. stirringwhile stirring
  6. customThe solvent is then removed in vacuo
  7. customthe product is absorbed on silica gel
  8. customIt is chromatographed (mobile phase: dichloromethane:methanol 30:1-20:1)
  9. custompurified by preparative RP-HPLC

Sources & evidence

ORD record
ord-94a6872eed0d475f87a75d8900ed75a9
Source dataset
uspto-grants-2006_11
Patent number
US07135474B2

Reaction notes

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