TMS-Imidazole → HCID 10183130, compound

HRID 1759679Notes

Reaction equation

HRID 1759679 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][C@H:8]([N:13]1[CH2:18][CH2:17][C:16]3([CH2:23][C@@H:22]([OH:24])[C:21]4[CH:25]=[C:26]([NH2:29])[CH:27]=[CH:28][C:20]=4[O:19]3)[CH2:15][CH2:14]1)[CH2:7][CH2:6]2)#[N:2].[CH3:30][Si:31](C1NC=CN=1)([CH3:33])[CH3:32]>C(#N)C>[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][C@H:8]([N:13]1[CH2:18][CH2:17][C:16]3([CH2:23][C@@H:22]([O:24][Si:31]([CH3:33])([CH3:32])[CH3:30])[C:21]4[CH:25]=[C:26]([NH2:29])[CH:27]=[CH:28][C:20]=4[O:19]3)[CH2:15][CH2:14]1)[CH2:7][CH2:6]2)#[N:2]

Participants

4

Reactant 2

HCID 14420972TMS-ImidazoleHCID 20748290HCID 20748290, compound

Product 1

HCID 10183130HCID 10183130, compoundYield 98.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of N-[1′-(6-cyano-1,2,3,4-tetrahydro-2(R)-naphthalenyl)-3,4-dihydro-4(R)-hydroxyspiro[2H-1-benzopyran-2,4′-piperidin]-6-yl]amine (50 mg, 0.128 mmole) in acetonitrile under argon was added trimethylsilylimidazole (0.36 gm, 2.5 mmole) and the reaction warmed to 60 C. for 1.5 hrs. The reaction was concentrated in vacuo and purified by flash chromatography using 95/5/0.1 dichloromethane/methanol/triethylamine to give N-[1′-(6-cyano-1,2,3,4-tetrahydro-2(R)-naphthalenyl)-3,4-dihydro-4(R)-trimethylsilyloxyspiro[2H-1-benzopyran-2,4′-piperidin]-6-yl]amine as a foam (58 mg, 98%). MS m/z 462 (M+), 1H NMR (CDCL3) δ 0.09 (9 H, s), 1.4-2.1 (8 H, m), 2.4-2.9 (9 H, m), 3.2 (2 H, br, s), 4.65 (1 H, t), 6.41(1 H, dd, J=9.2 and 3.3 Hz), 6.49 (1 H, d, J=3.3 Hz), 6.52 (1 H, d, J=9.2 Hz), 7.03 (1 H, d, J=9.2 Hz), 7.22 (2 H, m).

Workup

  1. temperaturethe reaction warmed to 60 C
  2. concentrationThe reaction was concentrated in vacuo
  3. custompurified by flash chromatography

Sources & evidence

ORD record
ord-620c17afa0d04879a76ecef7d7c1de33
Source dataset
uspto-grants-2005_01
Patent number
US06838291B2

Reaction notes

Loading…