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

HRID 639084Notes

Reaction equation

HRID 639084 reaction equation
Cl.[NH2:2][CH2:3][C:4]1([OH:24])[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][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])[CH2:5]1.[O:25]=[C:26]1[NH:31][C:30]2[N:32]=[C:33]([CH:36]=O)[CH:34]=[CH:35][C:29]=2[S:28][CH2:27]1.CCN(CC)CC.[BH4-].[Na+]>C(Cl)Cl.CCO>[F:23][C:12]1[CH:13]=[N:14][C:15]2[C:20]([C:11]=1[CH2:10][CH2:9][N:6]1[CH2:7][CH2:8][C:4]([CH2:3][NH:2][CH2:36][C:33]3[CH:34]=[CH:35][C:29]4[S:28][CH2:27][C:26](=[O:25])[NH:31][C:30]=4[N:32]=3)([OH:24])[CH2:5]1)=[N:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 115935913-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehydeHCID 68576769HCID 68576769, compound

Product 1

HCID 11634694(+/-)-6-({[(1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-hydroxy-3-pyrrolidinyl)methyl]amino}methyl)-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-oneYield 72%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 3-(aminomethyl)-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinol hydrochloride salt (0.21 mmole) in dry CH2Cl2 (25 mL) and dry EtOH (20 mL) at RT was added 3-oxo-3,4-dihydro-2H-pyrido[1,4]thiazine-6-carboxaldehyde (0.04 g, 0.21 mmole) and Et3N (0.06 mL, 0.42 mmole). After 24 h at RT was added NaBH4 (0.01 g, 0.23 mmole). After 2 h, silica gel (5 g) was added to the reaction solution and the suspension was concentrated under vacuum to a dry solid. Purification on silica (CHCl3/MeOH, 9:1 containing 5% NH4OH) afforded the title compound (0.075 g, 72%) as light yellow solid: 1H NMR (400 MHz, CDCl3) δ 8.51 (s, 1H), 8.08 (d, J=9.0 Hz, 1H), 7.54 (d, J=7.8 Hz, 1H), 7.00 (d, J=9.0 Hz, 1H), 6.88 (d, J=7.8 Hz, 1H), 4.38 (s, 2H), 4.03 (s, 3H), 3.81 (m, 2H), 3.37 (m, 4H), 3.12 (m, 4H), 2.72 (m, 2H), 2.54 (m, 2H), 1.92 (m, 2H). LC-MS (ES) m/e 499 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-405f4df3e8544959a6fc74464e55f983
Source dataset
uspto-grants-2010_04
Patent number
US07691850B2

Reaction notes

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