Tetrahydrofuran → 2,2-dimethylmalonic acid 5-{(4-{amino[2,2-dimethylbutoxycarbonylimino]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 2089667Notes

Reaction equation

HRID 2089667 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].[N+](C1C=CC([O:65][C:66](=O)[O:67][CH2:68][C:69]([CH3:73])([CH3:72])[CH2:70][CH3:71])=CC=1)([O-])=O.C1COCC1.C(N(CC)CC)C>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:46]=[CH:47][CH:48]=[CH:49][N:50]=2)[N:18]=[C:19]([CH:21]([NH:35][C:36]2[CH:37]=[CH:38][C:39]([C:42]([NH2:43])=[N:44][C:66]([O:67][CH2:68][C:69]([CH3:73])([CH3:72])[CH2:70][CH3:71])=[O:65])=[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

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 67469959Carbonic acid 2,2-dimethylbutyl 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 674711752,2-dimethylmalonic acid 5-{(4-{amino[2,2-dimethylbutoxycarbonylimino]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 176Acetic AcidSolvent

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 (270 mg), carbonic acid 2,2-dimethylbutyl ester 4-nitrophenyl ester (141 mg), and THF (10 mL), triethylamine (0.17 mL) was added, and the resulting mixture was stirred at room temperature for 26 hours. Acetic acid (0.3 mL) was added to the reaction solution, and the resulting mixture was concentrated under reduced pressure. The residue obtained was purified by NAM silica gel column chromatography (mixed solvent of methanol-ethyl acetate) to obtain the captioned compound.

Workup

  1. additionwas added
  2. concentrationthe resulting mixture was concentrated under reduced pressure
  3. customThe residue obtained
  4. customwas purified by NAM silica gel column chromatography (mixed solvent of methanol-ethyl acetate)
  5. customto obtain the captioned compound

Sources & evidence

ORD record
ord-0fe3db599f13488290aebdb772e1e67a
Source dataset
uspto-grants-2013_05
Patent number
US08436009B2

Reaction notes

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