Diisobutylaluminumhydride → [(R)-1-(4-Fluorophenyl)-6-[[6-(4-morpholinyl)-3-pyridinyl]sulfonyl]-1,4,7,8-tetrahydro-1,2,6-triazacyclopenta[b]naphthalen-4a-yl]methanol

HRID 1907274Notes

Reaction equation

HRID 1907274 reaction equation
C[O:2][C:3]([C@@:5]12[CH2:14][N:13]([S:15]([C:18]3[CH:19]=[N:20][C:21]([N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[CH:22][CH:23]=3)(=[O:17])=[O:16])[CH2:12][CH2:11][C:10]1=[CH:9][C:8]1[N:30]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=3)[N:31]=[CH:32][C:7]=1[CH2:6]2)=O.[H-].C([Al+]CC(C)C)C(C)C>ClCCl.C1(C)C=CC=CC=1.O>[F:39][C:36]1[CH:37]=[CH:38][C:33]([N:30]2[C:8]3[CH:9]=[C:10]4[C@:5]([CH2:3][OH:2])([CH2:6][C:7]=3[CH:32]=[N:31]2)[CH2:14][N:13]([S:15]([C:18]2[CH:19]=[N:20][C:21]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)=[CH:22][CH:23]=2)(=[O:16])=[O:17])[CH2:12][CH2:11]4)=[CH:34][CH:35]=1

Participants

6

Reactant 2

HCID 21225700DiisobutylaluminumhydrideHCID 66780158(R)-1-(4-fluorophenyl)-6-(6-morpholin-4-ylpyridine-3-sulfonyl)-1,4,5,6,7,8-hexahydro-1,2,6-triazacyclopenta[b]naphthalene-4a-carboxylic acid methyl ester

Product 1

HCID 66780233[(R)-1-(4-Fluorophenyl)-6-[[6-(4-morpholinyl)-3-pyridinyl]sulfonyl]-1,4,7,8-tetrahydro-1,2,6-triazacyclopenta[b]naphthalen-4a-yl]methanolYield 103.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (R)-1-(4-fluorophenyl)-6-(6-morpholin-4-ylpyridine-3-sulfonyl)-1,4,5,6,7,8-hexahydro-1,2,6-triazacyclopenta[b]naphthalene-4a-carboxylic acid methyl ester (17 g) in dichloromethane (300 mL) under nitrogen at −78° C. was treated with a 1.0 M solution of diisobutylaluminium hydride in toluene (123 mL). After 1 hour at −78° C., the solution was diluted with water and the phases separated. The organic phase was dried over sodium sulfate and concentrated under reduced pressure. The residue was triturated with diethyl ether to afford the title compound as a white solid (16.7 g). 1H NMR (CDCl3): δ 8.56-8.53 (d, 1H, J=2.4 Hz), 7.81-7.77 (dd, 1H, J=9.0, 2.4 Hz), 7.44-7.38 (m, 3H), 7.19-7.12 (m, 3H), 6.65-6.60 (d, 1H, J=9.0 Hz), 6.31-6.28 (d, 1H, J=2.5 Hz), 4.08-4.03 (dd, 1H, J=12, 2.4 Hz), 3.99-3.92 (m, 1H), 3.84-3.79 (m, 4H), 3.69-3.64 (m, 4H), 3.37-3.30 (m, 1H), 3.14-3.08 (d, 1H, J=16 Hz), 2.82-2.70 (m, 1H), 2.58-2.48 (m, 1H), 2.42-3.34 (m, 1H), 2.28-2.16 (m, 3H).

Workup

  1. customthe phases separated
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-fde98b32154a403eaa19a9b89f0e91d4
Source dataset
uspto-grants-2013_12
Patent number
US08598154B2

Reaction notes

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