Tetrahydrofuran → HCID 68519950, compound

HRID 1992408Notes

Reaction equation

HRID 1992408 reaction equation
[C:1](C=P(CCCC)(CCCC)CCCC)#N.[C:17]([C:19]1[CH:50]=[CH:49][C:22]([O:23][CH2:24][CH2:25][N:26]2[CH2:33][CH:32]3[O:34][CH:28]([CH2:29][N:30]([CH2:35][CH2:36][NH:37][S:38]([C:41]4[CH:46]=[CH:45][C:44]([F:47])=[CH:43][C:42]=4[F:48])(=[O:40])=[O:39])[CH2:31]3)[CH2:27]2)=[C:21]([F:51])[CH:20]=1)#[N:18].C1COCC1>CO>[C:17]([C:19]1[CH:50]=[CH:49][C:22]([O:23][CH2:24][CH2:25][N:26]2[CH2:33][CH:32]3[O:34][CH:28]([CH2:29][N:30]([CH2:35][CH2:36][N:37]([CH3:1])[S:38]([C:41]4[CH:46]=[CH:45][C:44]([F:47])=[CH:43][C:42]=4[F:48])(=[O:40])=[O:39])[CH2:31]3)[CH2:27]2)=[C:21]([F:51])[CH:20]=1)#[N:18]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 4622928CyanomethylenetributylphosphoraneHCID 68522068HCID 68522068, compound

Product 1

HCID 68519950HCID 68519950, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
160 °C

Procedure

Cyanomethylenetri-n-butylphosphorane (90%, 0.158 g, 0.59 mmol) was weighed into a microwave vial. N-(2-{7-[2-(4-Cyano-2-fluoro-phenoxy)-ethyl]-9-oxa-3,7-diaza-bicyclo[3.3.1]non-3-yl}-ethyl)-2,4-difluoro-benzenesulfonamide (100 mg, 0.2 mmol, from example 11 above) and THF (2 mL) were added. Methanol (16 μl, 0.39 mmol) was then added and the reaction was heated with microwave irradiation at 160° C. for 15 min. MeOH (1 mL) was added and the reaction was heated with microwave irradiation for a further 10 min in order to consume excess reagent. The reaction mixture was concentrated and the crude product was purified by chromatography on silica gel using methanol saturated with ammonia in dichloromethane as eluent. The product isolated could be purified further by recrystallisation from MeOH to give a solid (55 mg, 53%).

Workup

  1. temperaturethe reaction was heated with microwave irradiation for a further 10 min in order
  2. customto consume excess reagent
  3. concentrationThe reaction mixture was concentrated
  4. customthe crude product was purified by chromatography on silica gel
  5. customThe product isolated could
  6. custombe purified further by recrystallisation from MeOH

Sources & evidence

ORD record
ord-ce529dbf62f147dba27a05c603cec09c
Source dataset
uspto-grants-2010_01
Patent number
US07648985B2

Reaction notes

Loading…