Ammonia → HCID 66775458, compound

HRID 1256225Notes

Reaction equation

HRID 1256225 reaction equation
[F:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:3]=1[C:4]([NH:6][C:7]1[CH:8]=[N:9][NH:10][C:11]=1[C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)=O.[Cl-].[Cl-].C1(P)C=CC=CC=1.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.N>O>[F:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:3]=1[C:4]1[C:13]2[CH:14]=[C:15]([F:18])[CH:16]=[CH:17][C:12]=2[C:11]2[NH:10][N:9]=[CH:8][C:7]=2[N:6]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 14812Phosphorus oxide (P4O10)HCID 20975587HCID 20975587, compoundHCID 66770255HCID 66770255, compound

Product 1

HCID 66775458HCID 66775458, compoundYield 27.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
165 °C

Procedure

A 250 ml round-bottomed flask equipped with a magnetic stirrer and with a septum having a top-mounted argon intake is charged with 2.6 g of 2,6-difluoro-N-[5′(4-fluorophenyl)-1H-pyrazol-4-yl]benzamide, 60 ml of phenylphosphine dichloride and 17.5 g of phosphorus pentoxide. After 23 h of heating at 165° C., the mixture is cooled to RT and then poured into a mixture of 260 ml of water and 400 g of ice. The temperature rises to 40° C. The mixture is neutralized by slow addition of 120 ml of 28% aqueous ammonia. It is extracted with AcOEt, washed with saturated NaCl solution and dried over MgSO4, then concentrated under RP. The product is purified by flash chromatography on silica gel (15-40 μm), eluting with a mixture of DCM and methanol (99/1 by vol.), to give 680 mg of 5-(2,6-difluorophenyl)-7-fluoro-1H-pyrazolo[4,3-c]isoquinoline (cream solid). MS (E/I): m/z=299 (M+); 1H NMR: 7.34 (t, J=7.8 Hz, 2 H) 7.38 (broad m, 1 H) 7.70 (m, 1 H) 7.96 (broad t, J=9.1 Hz, 1 H) 8.48 (broad s, 1 H) 8.63 (dd, J=9.1, 5.6 Hz, 1 H) 14.29 (broad s, 1 H).

Workup

  1. customA 250 ml round-bottomed flask equipped with a magnetic stirrer and with a septum
  2. temperaturethe mixture is cooled to RT
  3. customrises to 40° C
  4. extractionIt is extracted with AcOEt
  5. washwashed with saturated NaCl solution
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under RP
  8. customThe product is purified by flash chromatography on silica gel (15-40 μm)
  9. washeluting with a mixture of DCM and methanol (99/1 by vol.)

Sources & evidence

ORD record
ord-ae5b3c45004044e690e243de819b320a
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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