2-fluoro-6-({2-[(2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide → HCID 178492997, compound

HRID 1014444Notes

Reaction equation

HRID 1014444 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([NH:11][C:12]2[C:13]3[CH:45]=[CH:44][N:43](S(C4C=CC(C)=CC=4)(=O)=O)[C:14]=3[N:15]=[C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:30][CH2:29][CH:28]([N:31]5[CH2:36][CH2:35][N:34]([S:37]([CH3:40])(=[O:39])=[O:38])[CH2:33][CH2:32]5)[CH2:27][CH2:26]4)=[CH:21][C:20]=3[O:41][CH3:42])[N:17]=2)[C:3]=1[C:4]([NH2:6])=[O:5]>O1CCOCC1>[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([NH:11][C:12]2[N:17]=[C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:30][CH2:29][CH:28]([N:31]5[CH2:36][CH2:35][N:34]([S:37]([CH3:40])(=[O:38])=[O:39])[CH2:33][CH2:32]5)[CH2:27][CH2:26]4)=[CH:21][C:20]=3[O:41][CH3:42])[NH:15][C:14]3=[N:43][CH:44]=[CH:45][C:13]=23)[C:3]=1[C:4]([NH2:6])=[O:5]

Participants

3

Reactant 1

HCID 594421352-fluoro-6-({2-[(2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide

Product 1

HCID 178492997HCID 178492997, compoundYield 44.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A suspension of 2-fluoro-6-({2-[(2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide (2.78 g, 3.51 mmol) and 1,4-dioxane (100 mL) in a 200 mL sealed flask was stirred in an 85° C. bath for 11 hours. The solution was extracted with ethyl acetate (200 mL) and brine (50 mL). The organic layers were dried over MgSO4, filtered, concentrated onto Celite and purified by SiO2 column chromatography (1-10% MeOH in CH2Cl2 and 0.1% NH4OH) to afford 2-fluoro-6-({2-[(2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-1H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide (1.0 g, 1.568 mmol, 44.7% yield). This material was combined in a 100mL round bottomed flask with approximately 600 mg of purified material from another batch. THF (10 mL) was added and the slurry was sonicated for 2 minutes. Ether (30 mL) was added and the slurry was sonicated for 2 minutes. The slurry was filtered and the solid collected. The solid was placed on the high vacuum pump at 0.5 torr for 2 hours to afford 2-fluoro-6-({2-[(2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-1H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide (1.4 g, 2.195 mmol). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.48-1.56 (m, 2H), 1.79-1.82 (m, 2H), 2.34-2.39 (m, 1H), 2.57-2.62 (m, 6H), 2.82 (s, 3H), 3.05-3.08 (m, 4H), 3.62-2.65 (m, 2H), 3.77 (s, 3H), 6.17 (s, 1H), 6.43 (dd, J=2.2, 8.7 Hz, 1H), 6.59 (d, J=2.0 Hz, 1H), 6.85-6.91 (m, 2H), 7.34-7.40 (m, 2H), 7.86 (d, J=8.6 Hz, 1H), 7.97 (s, 1H), 8.05 (s, 1H), 8.44 (d, J=8.4 Hz, 1H), 10.41 (s, 1H), 11.26 (s, 1H); ESIMS (M+H)+=638.

Workup

  1. customsealed flask
  2. extractionThe solution was extracted with ethyl acetate (200 mL) and brine (50 mL)
  3. dry with materialThe organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated onto Celite
  6. custompurified by SiO2 column chromatography (1-10% MeOH in CH2Cl2 and 0.1% NH4OH)

Sources & evidence

ORD record
ord-d53b985339ef405287d86aac5aa27c09
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

Loading…