1,1,3,3-Tetramethylguanidine → (Z)-2-[[4-[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]benzyl]amino]carbonyl]-2,6-dimethylbenzoyl]amino]-3-(2,4-dimethylthiazol-5-yl)propenoic acid methyl ester

HRID 1058418Notes

Reaction equation

HRID 1058418 reaction equation
CN(C)C(N(C)C)=N.[CH3:9][O:10][C:11](=[O:48])[CH:12](P(OC)(OC)=O)[NH:13][C:14](=[O:41])[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]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34])[CH:27]=2)=[O:23])=[CH:17][C:16]=1[CH3:40].[CH3:49][C:50]1[S:51][C:52]([CH:56]=O)=[C:53]([CH3:55])[N:54]=1>>[CH3:9][O:10][C:11](=[O:48])/[C:12](/[NH:13][C:14](=[O:41])[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]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:34])[CH3:35])[CH:27]=2)=[O:23])=[CH:17][C:16]=1[CH3:40])=[CH:56]/[C:52]1[S:51][C:50]([CH3:49])=[N:54][C:53]=1[CH3:55]

Participants

4

Reactant 3

HCID 664601,1,3,3-Tetramethylguanidine2×HCID 27762492,4-Dimethyl-1,3-thiazole-5-carbaldehydeHCID 23560782Rac.-n-[2,6-dimethyl-4-[[[3-[[(1,1-dimethylethyl) dimethylsilyl]oxy]benzyl]amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester

Product 1

HCID 70030107(Z)-2-[[4-[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]benzyl]amino]carbonyl]-2,6-dimethylbenzoyl]amino]-3-(2,4-dimethylthiazol-5-yl)propenoic acid methyl esterYield 51.3%

Conditions

Temperature
-40 °C

Procedure

1,1,3,3-Tetramethylguanidine (54 μL, 0.425 mmol) was added to a solution of rac.-2-(dimethoxyphosphinyl)-N-[4-[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]benzyl]amino]carbonyl]-2,6-dimethylbenzoyl]glycine methyl ester (Example 126; 150 mg, 0.25 mmol) in tetrahydrofiran (2 mL) at −40° C. The solution was stirred at −40° C. for 5 min and then 2,4-dimethylthiazol-5-carboxaldehyde (Example 43; 43 mg, 0.3 mmol) was added. The reaction mixture was stirred at −40° C. for 60 min and then allowed to stir at room temperature for 4 h. A second portion of 1,1,3,3-tetramethylguanidine (27 μL, 0.213 mmol) and the reaction was allowed to stir at room temperature for 2 days. The solution was partitioned between pH 6 phosphate buffer and ethyl acetate and the organic layer was dried (MgSO4), filtered and evaporated. The residue was chromatographed (silica gel, ethyl acetate in petroleum ether) to furnish 78 mg of (Z)-2-[[4-[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]benzyl]amino]carbonyl]-2,6-dimethylbenzoyl]amino]-3-(2,4-dimethylthiazol-5-yl)propenoic acid methyl ester as a colorless foam (50% yield).

Workup

  1. stirringThe reaction mixture was stirred at −40° C. for 60 min
  2. stirringto stir at room temperature for 4 h
  3. stirringto stir at room temperature for 2 days
  4. customThe solution was partitioned between pH 6 phosphate buffer and ethyl acetate
  5. dry with materialthe organic layer was dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was chromatographed (silica gel, ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-8650be61252e48adbfa860f1849b66e8
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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