Dimethylformamide → HCID 178509601, compound

HRID 353242Notes

Reaction equation

HRID 353242 reaction equation
[Cl:1][C:2]1[CH:19]=[C:18]([CH2:20][C:21](=O)[C:22]2[CH:26]=[C:25]([C:27](=[O:32])C(Cl)(Cl)Cl)[NH:24][CH:23]=2)[CH:17]=[CH:16][C:3]=1[CH2:4][N:5]1C(=O)C2C(=CC=CC=2)C1=O.[Cl:34][C:35]1[CH:36]=[C:37](NCCO)[CH:38]=[CH:39][C:40]=1[F:41].[C:46]([CH:50]([N:54](C)C)N(C)C)(C)(C)C.[OH2:57].[NH2:58]N.C[N:61]([CH:63]=O)C>C1COCC1.C(O)C>[Cl:34][C:35]1[CH:36]=[C:37]([CH:50]([NH:54][C:27]([C:25]2[NH:24][CH:23]=[C:22]([C:21]3[C:20]([C:18]4[CH:17]=[CH:16][C:3]([CH2:4][NH2:5])=[C:2]([Cl:1])[CH:19]=4)=[CH:63][NH:61][N:58]=3)[CH:26]=2)=[O:32])[CH2:46][OH:57])[CH:38]=[CH:39][C:40]=1[F:41]

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 24654Hydrazine hydrate (1:1)HCID 129886122-(2-Chloro-4-{2-oxo-2-[5-(2,2,2-trichloro-acetyl)-1H-pyrrol-3-yl-]-ethyl}-benzyl)-isoindole-1,3-dioneHCID 15731881Tert-butyl bis(dimethylamino)-methaneHCID 22349678N-2-hydroxyethyl-3-chloro-4-fluoroaniline

Product 1

HCID 178509601HCID 178509601, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of compound 10 (1.0 mmol) in DMF (5 mL) was added (S) 3-chloro-4-fluoro phenyl glycinol (1.2 mmol), then stirred for 15 h. The solvent was concentrated under vacuum. To the residue (1.0 mmol) in THF (1 mL) was added tert-butyl bis(dimethylamino)-methane (1 mL, 5 mmol). The mixture was stirred for 15 h at 50 ° C. and then concentrated under vacuum. To the residue (1 mmol) was added C2H5OH (5 mL) and hydrazine hydrate (1 mL, 20 mmol). The mixture was refluxed for 3 h and cooled to room temperature. The solvents were removed under vacuum and the crude products were purified from preparatory HPLC. This afforded the product 11 as a white solid. 1HNMR (CD3OD) 7.6 (s, 1H), 7.4 (s, 1H), 7.2-7.4 (m, 3H), 7.1-7.2 (m, 1H), 7.0 (t, 1H), 6.8 (d, 2H), 4.9 (t, 1H), 4.1 (s, 2H), 3.6 (dd, 2H).

Workup

  1. concentrationThe solvent was concentrated under vacuum
  2. stirringThe mixture was stirred for 15 h at 50 ° C.
  3. concentrationconcentrated under vacuum
  4. temperatureThe mixture was refluxed for 3 h
  5. customThe solvents were removed under vacuum
  6. customthe crude products were purified from preparatory HPLC

Sources & evidence

ORD record
ord-a8f6e88f2b724335ab854d3a5283726f
Source dataset
uspto-grants-2004_06
Patent number
US06750239B2

Reaction notes

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