1,1,3,3-Tetramethylguanidine → (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-(quinolin-3-yl)propenoic acid methyl ester

HRID 1058422Notes

Reaction equation

HRID 1058422 reaction equation
CN(C)C(N(C)C)=N.[CH3:9][O:10][C:11](=[O:41])[CH:12](P(OC)(OC)=O)[NH:13][C:14](=[O:34])[C:15]1[C:20]([CH3:21])=[CH:19][C:18]([C:22]([NH:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([OH:32])[CH:27]=2)=[O:23])=[CH:17][C:16]=1[Cl:33].[N:42]1[C:51]2[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=2)[CH:45]=[C:44]([CH:52]=O)[CH:43]=1>O1CCCC1>[CH3:9][O:10][C:11](=[O:41])/[C:12](/[NH:13][C:14](=[O:34])[C:15]1[C:20]([CH3:21])=[CH:19][C:18]([C:22]([NH:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([OH:32])[CH:27]=2)=[O:23])=[CH:17][C:16]=1[Cl:33])=[CH:52]/[C:44]1[CH:43]=[N:42][C:51]2[C:46]([CH:45]=1)=[CH:47][CH:48]=[CH:49][CH:50]=2

Participants

5

Reactant 3

HCID 664601,1,3,3-TetramethylguanidineHCID 836413-QuinolinecarboxaldehydeHCID 23560749Rac.-n-[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester

Product 1

HCID 59918694(Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-(quinolin-3-yl)propenoic acid methyl esterYield 56.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1,1,3,3-Tetramethylguanidine (30 μL, 0.24 mmol) was added to a solution of rac.-N-[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (Example 132; 55 mg, 0.11 mmol) in tetrahydrofuran (2 mL) at room temperature. After 5 min, quinoline-3-carboxaldehyde (18 mg, 0.114 mmol) was added and the solution was stirred at room temperature for 16 h. The reaction mixture was evaporated to dryness and the residue was dissolved in a solvent mixture of chloroform/methanol/water/acetic acid (150:30:10:6) and evaporated to dryness. A solution of the residue in a minimum amount of chloroform/methanol/water/acetic acid (150:30:10:6) was applied to a column of three piggy-backed SepPak Plus® silica gel cartridges that had been pre-washed with chloroform. The column was eluted with chloroform, then with a mixture of chloroform/methanol/water/acetic acid (300:30:10:6). Evaporation of the appropriate fractions gave (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-(quinolin-3-yl)propenoic acid methyl ester (32.7 mg, 55% yield) as a colorless powder.

Workup

  1. customThe reaction mixture was evaporated to dryness
  2. dissolutionthe residue was dissolved in a solvent mixture of chloroform/methanol/water/acetic acid (150:30:10:6)
  3. customevaporated to dryness
  4. washhad been pre-washed with chloroform
  5. washThe column was eluted with chloroform
  6. additionwith a mixture of chloroform/methanol/water/acetic acid (300:30:10:6)
  7. customEvaporation of the appropriate fractions

Sources & evidence

ORD record
ord-2607463aa5d94dcb83808b4420eaf861
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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