Sodium Carbonate → N-(3-fluoro-4-(2-(4-(methylcarbamoyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-1-methyl-2-oxopyrrolidine-3-carboxamide

HRID 1676345Notes

Reaction equation

HRID 1676345 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:19][C:20]([CH:22]2[CH2:26][CH2:25][N:24]([CH3:27])[C:23]2=[O:28])=[O:21])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16](I)[S:17][C:10]=12.[CH3:29][NH:30][C:31]([C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1)=[O:32].C([O-])([O-])=O.[Na+].[Na+]>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.COCCOC>[F:1][C:2]1[CH:3]=[C:4]([NH:19][C:20]([CH:22]2[CH2:26][CH2:25][N:24]([CH3:27])[C:23]2=[O:28])=[O:21])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:36]3[CH:37]=[CH:38][C:33]([C:31](=[O:32])[NH:30][CH3:29])=[CH:34][CH:35]=3)[S:17][C:10]=12

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27735264-(Methylcarbamoyl)benzeneboronic acidHCID 67349824N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-1-methyl-2-oxopyrrolidine-3-carboxamide

Product 1

HCID 58949488N-(3-fluoro-4-(2-(4-(methylcarbamoyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-1-methyl-2-oxopyrrolidine-3-carboxamideYield 26.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
60 °C

Procedure

A round-bottomed flask was charged with N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-1-methyl-2-oxopyrrolidine-3-carboxamide (20.0 mg, 0.039 mmol), 4-(methylcarbamoyl)phenylboronic acid (21.0 mg, 0.117 mmol), tetrakis(triphenylphosphine)palladium (9.04 mg, 0.0078 mmol), Na2CO3 (0.098 ml, 0.20 mmol) and DME (10 mL). The reaction mixture was stirred at 60° C. until the starting material had been consumed (overnight). Then the reaction mixture was cooled to room temperature and partitioned between EtOAc (100 mL) and H2O (100 mL). The phases were separated and the aqueous phase was re-extracted with EtOAc (3×100 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude product. The crude product was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1, v/v) to give product (5.3 mg, the yield is 26.1%). LRMS (APCI neg): >99% purity, 254 nm, m/e 517 (M−1). 1H NMR (400 MHz, DMSO-d6) δ 10.05 (s, 1H), 8.50 (m, 1H), 7.79-7.87 (m, 5H), 7.21-7.33 (m, 2H), 6.51 (d, 1H), 6.17 (d, 1H), 3.38-3.49 (m, 3H), 3.05 (d, 3H), 2.95 (s, 3H), 2.38-2.70 (m, 2H).

Workup

  1. customhad been consumed (overnight)
  2. temperatureThen the reaction mixture was cooled to room temperature
  3. custompartitioned between EtOAc (100 mL) and H2O (100 mL)
  4. customThe phases were separated
  5. extractionthe aqueous phase was re-extracted with EtOAc (3×100 mL)
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-1958b81b20f5471e94b807d81511f200
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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