Sodium triacetoxyborohydride → (3S,4S)-4-{[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]methyl}-1-{2-[6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinol

HRID 639119Notes

Reaction equation

HRID 639119 reaction equation
[NH2:1][CH2:2][C@H:3]1[CH2:7][N:6]([CH2:8][CH2:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[N:18]=3)[N:13]=[CH:12][CH:11]=2)[CH2:5][C@H:4]1[OH:22].[O:23]1[C:32]2[CH:31]=[C:30]([CH:33]=O)[N:29]=[CH:28][C:27]=2[O:26][CH2:25][CH2:24]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.CCO>[O:23]1[C:32]2[CH:31]=[C:30]([CH2:33][NH:1][CH2:2][C@H:3]3[CH2:7][N:6]([CH2:8][CH2:9][C:10]4[C:19]5[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[N:18]=5)[N:13]=[CH:12][CH:11]=4)[CH2:5][C@H:4]3[OH:22])[N:29]=[CH:28][C:27]=2[O:26][CH2:25][CH2:24]1

Participants

6

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 218736682,3-Dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehydeHCID 59026216(3S,4S)-4-(aminomethyl)-1-{2-[6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinol

Product 1

HCID 59026221(3S,4S)-4-{[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]methyl}-1-{2-[6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinolYield 27%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (3S,4S)-4-(aminomethyl)-1-{2-[6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinol (0.30 g, 1.0 mmole) in dry CH2Cl2 (25 mL) and dry EtOH (10 mL) at RT was added 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehyde (0.165 g, 1.0 mmole). After 24 h, at RT was added NaBH(OAc)3 (0.32 g, 1.5 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 (0.12 g, 27%) as light yellow solid: 1H NMR (400 MHz, CD3OD) δ 8.67 (d, J=4.5 Hz, 1H), 8.19 (d, J=9.0 Hz, 1H), 7.68 (d, J=4.5 Hz, 1H), 7.25 (d, J=9.0 Hz, 1H), 7.02 (s, 1H), 4.61 (m, 1H), 4.38 (m, 4H), 4.20 (s, 2H), 4.15 (s, 3H), 3.60 (m, 8H), 3.42 (m, 1H), 3.25 (m, 1H), 2.82 (m, 1H). LC-MS (ES) m/e 452 (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-855a74832cf540d0a6e8f28549b4f0d9
Source dataset
uspto-grants-2010_04
Patent number
US07691850B2

Reaction notes

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