Dimethylacetamide → 2,2-dimethylmalonic acid 5-{(R)-(4-{amino(2,2-dimethylpropoxylcarbonylimino)methyl}phenylamino)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]methyl}-2-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yloxymethyl ester 2,2-dimethylpropyl ester

HRID 2089648Notes

Reaction equation

HRID 2089648 reaction equation
C(O)(=O)C.[CH3:5][C:6]([CH3:55])([CH3:54])[CH2:7][O:8][C:9](=[O:53])[C:10]([CH3:52])([CH3:51])[C:11]([O:13][CH2:14][O:15][C:16]1[N:17]([C:45]2[N:50]=[CH:49][CH:48]=[CH:47][N:46]=2)[N:18]=[C:19]([CH:21]([NH:35][C:36]2[CH:41]=[CH:40][C:39]([C:42](=[NH:44])[NH2:43])=[CH:38][CH:37]=2)[C:22]2[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[C:24]([O:30][CH2:31][CH2:32][OH:33])[C:23]=2[F:34])[N:20]=1)=[O:12].CC(N(C)C)=O.[N+](C1C=CC([O:71][C:72](=O)[O:73][CH2:74][C:75]([CH3:78])([CH3:77])[CH3:76])=CC=1)([O-])=O>C(N(CC)CC)C>[CH3:5][C:6]([CH3:55])([CH3:54])[CH2:7][O:8][C:9](=[O:53])[C:10]([CH3:52])([CH3:51])[C:11]([O:13][CH2:14][O:15][C:16]1[N:17]([C:45]2[N:46]=[CH:47][CH:48]=[CH:49][N:50]=2)[N:18]=[C:19]([C@H:21]([NH:35][C:36]2[CH:37]=[CH:38][C:39]([C:42]([NH2:43])=[N:44][C:72]([O:73][CH2:74][C:75]([CH3:78])([CH3:77])[CH3:76])=[O:71])=[CH:40][CH:41]=2)[C:22]2[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[C:24]([O:30][CH2:31][CH2:32][OH:33])[C:23]=2[F:34])[N:20]=1)=[O:12]

Participants

5

Reactant 3

HCID 31374DimethylacetamideHCID 22389509Carbonic acid 2,2-dimethylpropyl ester 4-nitrophenyl esterHCID 866773942,2-dimethylmalonic acid 5-{(4-carbamimidoylphenylamino)-[2-fluoro-3-(2-hydroxyethoxy)-5-metho xyphenyl]methyl}-2-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yloxymethyl ester 2,2-dimethylpropyl ester acetate

Product 1

HCID 674705372,2-dimethylmalonic acid 5-{(R)-(4-{amino(2,2-dimethylpropoxylcarbonylimino)methyl}phenylamino)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]methyl}-2-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yloxymethyl ester 2,2-dimethylpropyl ester

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

To a mixture of 2,2-dimethylmalonic acid 5-{(4-carbamimidoylphenylamino)-[2-fluoro-3-(2-hydroxyethoxy)-5-metho xyphenyl]methyl}-2-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yloxymethyl ester 2,2-dimethylpropyl ester acetate (Example 18e, 70 mg) and DMA (2 mL), carbonic acid 2,2-dimethylpropyl ester 4-nitrophenyl ester [CAS No. 158810-98-1] (70 mg) and triethylamine (0.07 mL) were added, and the resulting mixture was stirred overnight at room temperature. The reaction solution was concentrated under reduced pressure. The residue obtained was purified by silica gel column chromatography (mixed solvent of heptane-ethyl acetate) to obtain a racemate of the captioned compound.

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure
  2. customThe residue obtained
  3. customwas purified by silica gel column chromatography (mixed solvent of heptane-ethyl acetate)
  4. customto obtain a racemate of the captioned compound

Sources & evidence

ORD record
ord-84d87480f56b4f7e895c7e15129469dd
Source dataset
uspto-grants-2013_05
Patent number
US08436009B2

Reaction notes

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