Acetonitrile → HCID 44223391, compound

HRID 2196669Notes

Reaction equation

HRID 2196669 reaction equation
[F:1][C:2]1[C:29]([NH:30][S:31]([CH2:34][CH2:35][CH3:36])(=[O:33])=[O:32])=[CH:28][CH:27]=[C:26]([F:37])[C:3]=1[C:4]([NH:6][C:7]1[CH:8]=[C:9]2[C:15](I)=[CH:14][N:13](S(C3C=CC=CC=3)(=O)=O)[C:10]2=[N:11][CH:12]=1)=[O:5].[F:38][C:39]1[CH:40]=[C:41](B(O)O)[CH:42]=[CH:43][C:44]=1[F:45].C([O-])([O-])=O.[K+].[K+].C(#N)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[F:38][C:39]1[CH:40]=[C:41]([C:15]2[C:9]3[C:10](=[N:11][CH:12]=[C:7]([NH:6][C:4](=[O:5])[C:3]4[C:26]([F:37])=[CH:27][CH:28]=[C:29]([NH:30][S:31]([CH2:34][CH2:35][CH3:36])(=[O:33])=[O:32])[C:2]=4[F:1])[CH:8]=3)[NH:13][CH:14]=2)[CH:42]=[CH:43][C:44]=1[F:45]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 27343373,4-Difluorobenzeneboronic acidHCID 67155879HCID 67155879, compound

Product 1

HCID 44223391HCID 44223391, compoundYield 44.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
160 °C

Procedure

2,6-Difluoro-N-(3-iodo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-3-(propylsulfonamido)benzamide (0.025 g, 0.038 mmol), 3,4-difluorophenylboronic acid (0.0090 g, 0.057 mmol), K2CO3 (0.026 g, 0.19 mmol), and Pd(PPh3)4 (0.0022 g, 0.0019 mmol) were taken up in 4:1 acetonitrile (“ACN”)/water (1.5 mL) and degassed with argon for 10 minutes. The reaction mixture was heated to 160° C. for 10 minutes under microwave irradiation. The solution was partitioned between water and EtOAc. The organic portion was washed with water (3×), brine, dried over Na2SO4 and concentrated to an oil. DCM was added to the oil, and a solid precipitated out, which was collected by filtration giving N-(3-(3,4-difluorophenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-2,6-difluoro-3-(propylsulfonamido)benzamide (8.5 mg, 44%). 1H NMR (400 MHz, DMSO-d6) δ 12.08 (br s, 1H), 10.97 (s, 1H), 9.80 (br s, 1H), 8.66 (br s, 1H), 8.52 (br s, 1H), 7.99 (br s, 1H), 7.69-7.75 (m, 1H), 7.51-7.59 (m, 3H), 7.25-7.30 (m, 1H), 3.11-3.15 (m, 2H), 1.74-1.80 (m, 2H), 0.98-1.02 (m, 3H); m/z (APCI-pos) M+1=505.2.

Workup

  1. customdegassed with argon for 10 minutes
  2. customThe solution was partitioned between water and EtOAc
  3. washThe organic portion was washed with water (3×), brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated to an oil
  6. additionDCM was added to the oil
  7. customa solid precipitated out
  8. filtrationwhich was collected by filtration

Sources & evidence

ORD record
ord-e36d859ab4604ba891005af986c21b20
Source dataset
uspto-grants-2012_12
Patent number
US08338452B2

Reaction notes

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