Sodium borohydride → 6-({[(1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-azetidinyl)methyl]amino}methyl)-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-one

HRID 1441261Notes

Reaction equation

HRID 1441261 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH2:12][CH2:13][N:14]1[CH2:17][CH:16]([CH2:18][NH2:19])[CH2:15]1)=[N:9][C:8]([O:20][CH3:21])=[CH:7][CH:6]=2.[O:22]=[C:23]1[NH:28][C:27]2[N:29]=[C:30]([CH:33]=O)[CH:31]=[CH:32][C:26]=2[S:25][CH2:24]1.[BH4-].[Na+]>C(Cl)Cl.CCO>[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH2:12][CH2:13][N:14]1[CH2:15][CH:16]([CH2:18][NH:19][CH2:33][C:30]3[CH:31]=[CH:32][C:26]4[S:25][CH2:24][C:23](=[O:22])[NH:28][C:27]=4[N:29]=3)[CH2:17]1)=[N:9][C:8]([O:20][CH3:21])=[CH:7][CH:6]=2

Participants

6

Reactant 3

HCID 4311764Sodium borohydrideHCID 115935913-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehydeHCID 58989533[(1-{2-[3-Fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-azetidinyl)methyl]amine

Product 1

HCID 115835896-({[(1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-azetidinyl)methyl]amino}methyl)-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-oneYield 109%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of [(1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-azetidinyl)methyl]amine (138 mg, 0.47 mmole) in dry CH2Cl2 (40 mL) and dry EtOH (5 mL) at RT was added 3-oxo-3,4-dihydro-2H-pyrido[1,4]thiazine-6-carboxaldehyde (91 mg, 0.47 mmole). After 12 h, NaBH4 was added to the reaction solution. After 4 hrs, silica gel was added to the reaction contents and the slurry was concentrated under vacuum to a dry solid. Purification on silica (CHCl3/MeOH, 9:1 containing 5% NH4OH) afforded the title compound (0.24 g, 50%) as light yellow solid: 1H NMR (400 MHz, CDCl3) δ 8.59 (1H, s), 8.17 (1H, d, J=9.0 Hz), 7.55 (1H, d, J=7.8 Hz), 7.04 (1H, d, J=9.0 Hz), 6.93 (1H, d, J=7.8 Hz), 4.08 (3H, s), 3.79 (2H, s), 3.51 (2H, t, J=7.4 Hz), 3.44 (2H, s), 3.22 (2H, app t), 2.95 (2H, t, J=6.7 Hz), 2.82 (4H, m), 2.65 (1H, m). LC-MS (ES) m/e 467 (M+H)+.

Workup

  1. waitAfter 4 hrs
  2. additionsilica gel was added to the reaction contents
  3. concentrationthe slurry was concentrated under vacuum to a dry solid
  4. customPurification on silica (CHCl3/MeOH, 9:1 containing 5% NH4OH)

Sources & evidence

ORD record
ord-03577094982c4081a781e4bf352c02e6
Source dataset
uspto-grants-2010_02
Patent number
US07655648B2

Reaction notes

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