(2S)-2-[5-ethoxy-2-fluoro-3-(1-methylpiperidin-4-yl)oxyphenyl]-2-[4-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]anilino]acetic acid → (S)-(4-carbamimidoyl-phenylamino)-[5-ethoxy-2-fluoro-3-(1-methyl-piperidin-4-yloxy)-phenyl]-acetic acid

HRID 478972Notes

Reaction equation

HRID 478972 reaction equation
C(OC([NH:8][C:9](=[NH:39])[C:10]1[CH:15]=[CH:14][C:13]([NH:16][C@@H:17]([C:21]2[CH:26]=[C:25]([O:27][CH2:28][CH3:29])[CH:24]=[C:23]([O:30][CH:31]3[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]3)[C:22]=2[F:38])[C:18]([OH:20])=[O:19])=[CH:12][CH:11]=1)=O)(C)(C)C>O.C(O)=O>[C:9]([C:10]1[CH:15]=[CH:14][C:13]([NH:16][C@@H:17]([C:21]2[CH:26]=[C:25]([O:27][CH2:28][CH3:29])[CH:24]=[C:23]([O:30][CH:31]3[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]3)[C:22]=2[F:38])[C:18]([OH:20])=[O:19])=[CH:12][CH:11]=1)(=[NH:8])[NH2:39]

Participants

3

Reactant 1

HCID 140461952(2S)-2-[5-ethoxy-2-fluoro-3-(1-methylpiperidin-4-yl)oxyphenyl]-2-[4-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]anilino]acetic acid

Product 1

HCID 69924164(S)-(4-carbamimidoyl-phenylamino)-[5-ethoxy-2-fluoro-3-(1-methyl-piperidin-4-yloxy)-phenyl]-acetic acidYield 72.1%

Reagents, catalysts & solvents 1

HCID 18673298Formic acid--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

A solution of 5.1 g (S)-[4-(tert-butoxycarbonylamino-imino-methyl)-phenylamino]-[5-ethoxy-2-fluoro-3-(1-methyl-piperidin-4-yloxy)-phenyl]-acetic acid in 102 ml water/formic acid 1:1 was heated to 40° C. for 2.5 hrs. The solvents were evaporated in vacuo, the residue dissolved in water and the solution evaporated again (repeated twice). The residue was dissolved in methanol and 7N methanolic ammonia was added until pH=9, wereby a precipitate was formed. The mixture was cooled to 0° C., the solid isolated by suction filtration and dried. Afterwards it was suspended in water and the pH adjusted to 9 wiTh conc. ammonia. Suction filtration and drying gave 3 g (S)-(4-carbamimidoyl-phenylamino)-[5-ethoxy-2-fluoro-3-(1-methyl-piperidin-4-yloxy)-phenyl]-acetic acid. White solid. Mp.: 269° C. MS: 445 ([M+H]+).

Workup

  1. customThe solvents were evaporated in vacuo
  2. dissolutionthe residue dissolved in water
  3. customthe solution evaporated again (
  4. dissolutionThe residue was dissolved in methanol
  5. addition7N methanolic ammonia was added until pH=9
  6. customwereby a precipitate was formed
  7. customthe solid isolated by suction filtration
  8. customdried
  9. filtrationSuction filtration
  10. customdrying

Sources & evidence

ORD record
ord-d4bb617031144f8caedfb59221eb1e30
Source dataset
uspto-grants-2003_11
Patent number
US06642386B2

Reaction notes

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