1-Hydroxybenzotriazole → N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxopyrrolidine-3-carboxamide

HRID 1676347Notes

Reaction equation

HRID 1676347 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[CH:16]=[C:17]([I:19])[S:18][C:11]=12)[NH2:5].[O:20]=[C:21]1[CH:25]([C:26](O)=[O:27])[CH2:24][CH2:23][NH:22]1.Cl.C(N=C=NCCCN(C)C)C.N1(O)C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([NH:5][C:26]([CH:25]2[CH2:24][CH2:23][NH:22][C:21]2=[O:20])=[O:27])[CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[CH:16]=[C:17]([I:19])[S:18][C:11]=12

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 134743702-Oxopyrrolidine-3-carboxylic acidHCID 584749503-Fluoro-4-((2-iodothieno[3,2-b]pyridin-7-yl)oxy)aniline

Product 1

HCID 67346994N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxopyrrolidine-3-carboxamideYield 44.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A flask was charged with 3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)aniline (Example 6, Step A, 150.0 mg, 0.388 mmol), 2-oxopyrrolidine-3-carboxylic acid (100.3 mg, 0.777 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (223.4 mg, 1.17 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (157.5 mg, 1.17 mmol), N-ethyl-N-isopropylpropan-2-amine (0.347 ml, 1.94 mmol) and THF (100 mL). The reaction mixture was stirred at room temperature until the starting material had been consumed (overnight). Then the reaction mixture was 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 (EtOAc/Hexane from 1/4 to 4/1, v/v) to afford product (85.0 mg, 44%). LRMS (APCI pos): >97% purity, 254 nm, m/e 498 (M+1).

Workup

  1. customhad been consumed (overnight)
  2. customThen the reaction mixture was partitioned between EtOAc (100 mL) and H2O (100 mL)
  3. customThe phases were separated
  4. extractionthe aqueous phase was re-extracted with EtOAc (3×100 mL)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield a crude product
  9. customThe crude product was purified by silica gel chromatography (EtOAc/Hexane from 1/4 to 4/1

Sources & evidence

ORD record
ord-1ab6280659224f55a6d33ac1146d2d0b
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

Loading…