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Methanol → 1,1-Dimethylethyl {1-[(3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-4-piperidinyl}carbamate

HRID 15314
Notes
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Reaction equation

HRID 15314 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH:12]([CH2:28]O)[CH2:13][N:14]1[CH2:19][CH2:18][CH:17]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:16][CH2:15]1)=[N:9][C:8]([O:30]C)=[CH:7][CH:6]=2.CO.C(N(CC)CC)C.CS(OS(C)(=O)=O)(=O)=O>ClCCl>[F:1][C:2]1[CH:3]=[N:4][C:5]2[CH:6]=[CH:7][C:8](=[O:30])[N:9]3[CH2:28][CH:12]([CH2:13][N:14]4[CH2:19][CH2:18][CH:17]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:24])([CH3:25])[CH3:26])[CH2:16][CH2:15]4)[C:11]=1[C:10]=23
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 887MethanolHCID 8471TriethylamineHCID 81560Methanesulfonic anhydrideHCID 574868741,1-Dimethylethyl (1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-3-hydroxypropyl}-4-piperidinyl)carbamate

Product 1

HCID 866305801,1-Dimethylethyl {1-[(3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-4-piperidinyl}carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
55 °C

Procedure

A solution of 1,1-dimethylethyl (1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-3-hydroxypropyl}-4-piperidinyl)carbamate (18.28 g, containing some non-alcohol impurity and a little MeOH, judged to contain 40 mmol alcohol-containing compounds) in dichloromethane (180 ml) was stirred under argon, ice-cooled and treated with triethylamine (11.1 ml, 80 mmol) and methanesulfonic anhydride (8.7 g, 50 mmol). After 1 hour the solution was heated to reflux for 2 days, evaporated and redissolved in chloroform (180 ml). This solution was heated under argon at 55° C. for 3 days, cooled, washed with aqueous sodium bicarbonate and the aqueous twice re-extracted with chloroform. The combined organic phases were dried and evaporated. Chromatography of the residue (methanol/dichloromethane gradient) and rechromatography of some impure fractions gave the product (13.35 g, containing 12.5% dichloromethane by weight).

Workup

  1. temperatureice-cooled
  2. temperatureAfter 1 hour the solution was heated
  3. temperatureto reflux for 2 days
  4. customevaporated
  5. dissolutionredissolved in chloroform (180 ml)
  6. temperaturecooled
  7. washwashed with aqueous sodium bicarbonate
  8. extractionthe aqueous twice re-extracted with chloroform
  9. customThe combined organic phases were dried
  10. customevaporated
  11. customChromatography of the residue (methanol/dichloromethane gradient) and rechromatography of some impure fractions gave

Sources & evidence

ORD record
ord-c1c7650d65dd45f29fe9498d2656c2ac
Source dataset
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07732461B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes