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

HRID 1676344Notes

Reaction equation

HRID 1676344 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].[CH3:20][N:21]1[CH2:25][CH2:24][CH:23]([C:26](O)=[O:27])[C:22]1=[O:29].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:23]2[CH2:24][CH2:25][N:21]([CH3:20])[C:22]2=[O:29])=[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 148766891-Methyl-2-oxopyrrolidine-3-carboxylic acidHCID 584749503-Fluoro-4-((2-iodothieno[3,2-b]pyridin-7-yl)oxy)aniline

Product 1

HCID 67349824N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-1-methyl-2-oxopyrrolidine-3-carboxamideYield 80.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A round-bottomed flask was charged with 3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)aniline (Example 6, Step A, 200.0 mg, 0.5179 mmol), 1-methyl-2-oxopyrrolidine-3-carboxylic acid (148.3 mg, 1.04 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (297.8 mg, 1.55 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (209.9 mg, 1.55 mmol), N-ethyl-N-isopropylpropan-2-amine (334.7 mg, 2.59 mmol) and THF (25 mL). The reaction mixture was stirred at room temperature until the starting material had been consumed (overnight). Then the reaction 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 (dichloromethane/7 M NH3 in MeOH from 100/1 to 10/1, v/v) to afford product (213 mg, 80.4%). LRMS (APCI pos) m/e 512 (M+1). 1H NMR (400 MHz, CDCl3) δ 10.06 (s, 1H), 8.42 (d, 1H), 7.79 (dd, 1H), 7.76 (s, 1H), 7.29 (m, 1H), 7.19 (t, 1H), 6.45 (dd, 1H), 3.43-3.49 (m, 3H), 2.94 (s, 3H), 2.36-2.61 (m, 2H).

Workup

  1. customhad been consumed (overnight)
  2. customThen the reaction 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 (dichloromethane/7 M NH3 in MeOH from 100/1 to 10/1

Sources & evidence

ORD record
ord-0bd8a8df2aea42ea986c53f32df9510c
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

Loading…