Ethanol → HCID 178515433, compound

HRID 1177020Notes

Reaction equation

HRID 1177020 reaction equation
[I:1][C:2]1[CH:17]=[CH:16][C:5]2[NH:6][C:7]([CH2:12][C:13](O)=[O:14])=[N:8][S:9](=[O:11])(=[O:10])[C:4]=2[CH:3]=1.C([O:21][C:22]([C:24]1[N:25]([NH:29][CH2:30][C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=2)[CH:26]=[CH:27][CH:28]=1)=O)C=C.[O-]CC.[Na+].C(O)C>ClCCl.CO.CN(C)C=O>[F:37][C:34]1[CH:33]=[CH:32][C:31]([CH2:30][N:29]2[C:13](=[O:14])[C:12]([C:7]3[NH:6][C:5]4[CH:16]=[CH:17][C:2]([I:1])=[CH:3][C:4]=4[S:9](=[O:11])(=[O:10])[N:8]=3)=[C:22]([OH:21])[C:24]3=[CH:28][CH:27]=[CH:26][N:25]23)=[CH:36][CH:35]=1

Participants

8

Reactant 4

HCID 702EthanolHCID 2723922Sodium ethoxideHCID 59853574(7-Iodo-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-acetic acidHCID 598535761-(4-fluoro-benzylamino)-1H-pyrrole-2-carboxylic acid allyl ester

Product 1

HCID 178515433HCID 178515433, compoundYield 64%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

N,N-Dicyclohexylcarbodiimide (4.33 mL of a 1.0 M solution in dichloromethane, 4.33 mmol) was added to a solution of (7-iodo-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (Example 4b, 1.58 g, 4.32 mmol) and 1-(4-fluoro-benzylamino)-1H-pyrrole-2-carboxylic acid allyl ester (Example 9a, 1.08 g, 3.94 mmol) in a 4:1 mixture of dichloromethane and N,N-dimethylformamide (25 mL) at 25° C. The reaction mixture was stirred at 25° C. for 2.5 h then was filtered. The filtrate was concentrated in vacuo and the residue was dissolved in ethanol (20 mL) at 25° C. A 21% solution of sodium ethoxide in ethanol (8.0 mL, 24.6 mmol) was added and the reaction mixture was heated at 80° C. for 8 h. After cooling to 25° C., the mixture was partitioned between 1.0 M aqueous hydrochloric acid solution (150 mL) and ethyl acetate (2×150 mL). The organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give a dark solid. Trituration of this material with methanol afforded a grey solid that was collected by vacuum filtration to afford the desired product, 1-(4-fluoro-benzyl)-4-hydroxy-3-(7-iodo-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-pyrrolo[1,2-b]pyridazin-2-one (1.42 g, 2.52 mmol, 64% yield). 1H NMR (400 MHz, DMSO-d6) δ: 5.64 (2H, s), 6.58-6.60 (1H, m), 7.01-7.02 (1H, m), 7.14-7.18 (2H, m), 7.42-7.46 (2H, m), 7.70-7.70 (1H, m), 8.02-8.04 (1H, m), 8.12-8.12 (1H, m), 13.70 (1H, s).

Workup

  1. filtrationthen was filtered
  2. concentrationThe filtrate was concentrated in vacuo
  3. dissolutionthe residue was dissolved in ethanol (20 mL) at 25° C
  4. temperaturethe reaction mixture was heated at 80° C. for 8 h
  5. temperatureAfter cooling to 25° C.
  6. customthe mixture was partitioned between 1.0 M aqueous hydrochloric acid solution (150 mL) and ethyl acetate (2×150 mL)
  7. dry with materialThe organic layers were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a dark solid
  11. filtrationthat was collected by vacuum filtration

Sources & evidence

ORD record
ord-4ee59577701a430687ce7700761979b3
Source dataset
uspto-grants-2010_11
Patent number
US07842838B2

Reaction notes

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