Sodium Sulfate → 6-({[((3S)-1-{(2R)-2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-2-hydroxyethyl}-3-pyrrolidinyl)methyl]amino}methyl)-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-one

HRID 639080Notes

Reaction equation

HRID 639080 reaction equation
[NH2:1][CH2:2][C@@H:3]1[CH2:7][CH2:6][N:5]([CH2:8][C@@H:9]([C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([O:21][CH3:22])[N:19]=3)[N:14]=[CH:13][C:12]=2[F:23])[OH:10])[CH2:4]1.[O:24]=[C:25]1[CH2:30][S:29][C:28]2[CH:31]=[CH:32][C:33]([CH:35]=O)=[N:34][C:27]=2[NH:26]1.[O-]S([O-])(=O)=O.[Na+].[Na+].[BH4-].[Na+]>C(Cl)Cl.CCO>[F:23][C:12]1[CH:13]=[N:14][C:15]2[C:20]([C:11]=1[C@@H:9]([OH:10])[CH2:8][N:5]1[CH2:6][CH2:7][C@@H:3]([CH2:2][NH:1][CH2:35][C:33]3[CH:32]=[CH:31][C:28]4[S:29][CH2:30][C:25](=[O:24])[NH:26][C:27]=4[N:34]=3)[CH2:4]1)=[N:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2

Participants

7

Reactant 4

HCID 24436Sodium SulfateHCID 4311764Sodium borohydrideHCID 115935913-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehydeHCID 59026145(1R)-2-[(3S)-3-(aminomethyl)-1-pyrrolidinyl]-1-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethanol

Product 1

HCID 590261046-({[((3S)-1-{(2R)-2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-2-hydroxyethyl}-3-pyrrolidinyl)methyl]amino}methyl)-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-oneYield 3.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (1R)-2-[(3S)-3-(aminomethyl)-1-pyrrolidinyl]-1-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethanol (90 mg, 0.28 mmol) in dry CH2Cl2 (2 mL) and dry EtOH (2 mL) was added 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carboxaldehyde (55 mg, 0.28 mmol) along with Na2SO4 (350 mg, 2.46 mmol). After 18 h at room temperature, NaBH4 (24 mg, 0.56 mmol) was added. After 2 h, the solution wa partitioned between ethyl acetate and the aqueous solution of sodium bicarbonate. The aqueous solution was extreacted several times with ethyl acetate. The organic fraction were pooled, concentrated and purified with column chromatography (silica, 0-8% MeOH in DCM (1% NH4OH)) affording a light yellow solid, which was completed with chiral purification. The title compound (5 mg, 3.6%) was provided as a white solid: LC/MS (ES) m/e 499 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 8.56 (s, 1H), 8.14 (d, J=9.0 Hz, 1H), 7.57 (d, J=7.6 Hz, 1H), 7.10 (d, J=9.2 Hz, 1H), 6.89 (d, J=7.6 Hz, 1H), 5.82-5.84 (m, 1H), 4.03 (s, 3H), 3.64 (s, 2H), 3.39-3.41 (m, 1H), 3.09-3.12 (m, 1H), 2.87-3.07 (m, 2H), 2.59-2.67 (m, 2H), 2.48-2.52 (m, 2H), 2.28-2.36 (m, 2H), 1.86-1.97 (m, 1H), 1.37-1.46 (m, 1H), 1.16-1.18 (m, 1H).

Workup

  1. waitAfter 2 h
  2. customthe solution wa partitioned between ethyl acetate
  3. concentrationconcentrated
  4. custompurified with column chromatography (silica, 0-8% MeOH in DCM (1% NH4OH))
  5. customaffording a light yellow solid, which
  6. customwas completed with chiral purification

Sources & evidence

ORD record
ord-4faeeaebf7fa43de94bc77caf6a09df7
Source dataset
uspto-grants-2010_04
Patent number
US07691850B2

Reaction notes

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