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

HRID 639103Notes

Reaction equation

HRID 639103 reaction equation
[F:1][C@H:2]1[CH2:6][N:5]([CH2:7][CH2:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([O:19][CH3:20])[N:17]=3)[N:12]=[CH:11][C:10]=2[F:21])[CH2:4][C@H:3]1[CH2:22][NH2:23].[O:24]=[C:25]1[NH:30][C:29]2[N:31]=[C:32]([CH:35]=O)[CH:33]=[CH:34][C:28]=2[S:27][CH2:26]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.CCO>[F:1][C@H:2]1[CH2:6][N:5]([CH2:7][CH2:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([O:19][CH3:20])[N:17]=3)[N:12]=[CH:11][C:10]=2[F:21])[CH2:4][C@H:3]1[CH2:22][NH:23][CH2:35][C:32]1[CH:33]=[CH:34][C:28]2[S:27][CH2:26][C:25](=[O:24])[NH:30][C:29]=2[N:31]=1

Participants

6

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 115935913-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehydeHCID 86616806HCID 86616806, compound

Product 1

HCID 86616805(+/-)-6-({[(cis-4-fluoro-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinyl)methyl]amino}methyl)-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-oneYield 46%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (±)-[(cis-4-fluoro-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinyl)methyl]amine (0.15 g, 0.46 mmole) in dry CH2Cl2 (25 mL) and dry EtOH (10 mL) at RT was added 3-oxo-3,4-dihydro-2H-pyrido[1,4]thiazine-6-carboxaldehyde (0.077 g, 0.46 mmole). After 24 h, at RT was added NaBH(OAc)3 (0.15 g, 0.69 mmole). After 2 h, the reaction solution was concentrated under vacuum and purified on silica (CHCl3/MeOH, 9:1 containing 5% NH4OH) to afford the title compound (0.10 g, 46%) as light yellow solid: 1H NMR (400 MHz, CDCl3) δ 8.67 (s, 1H), 8.21 (d, J=9.1 Hz, 1H), 7.60 (d, J=7.8 Hz, 1H), 7.10 (m, 2H), 4.13 (s, 2H), 4.10 (s, 3H), 3.62 (m, 2H), 3.49-3.43 (m, 6H), 3.21 (m, 2H), 2.99 (m, 2H), 2.32 (app s, 2H). LC-MS (ES) m/e 501 (M+H)+.

Workup

  1. waitAfter 2 h
  2. concentrationthe reaction solution was concentrated under vacuum
  3. custompurified on silica (CHCl3/MeOH, 9:1 containing 5% NH4OH)

Sources & evidence

ORD record
ord-be44a4c2aabd4ffdaf125c3de5dea1e2
Source dataset
uspto-grants-2010_04
Patent number
US07691850B2

Reaction notes

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