Sodium Hydroxide → (2,3-Dihydro-benzo[1,4]dioxin-6-ylmethyl)-{2-[2-(2-imidazol-1-yl-6-methyl-pyrimidin-4-yl)-pyrrolidin-1-yl]-ethyl}-amine

HRID 1170520Notes

Reaction equation

HRID 1170520 reaction equation
[N:1]1([C:6]2[N:11]=[C:10]([CH:12]3[CH2:16][CH2:15][CH2:14][N:13]3[CH2:17][CH2:18][NH2:19])[CH:9]=[C:8]([CH3:20])[N:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.[O:21]1[C:26]2[CH:27]=[CH:28][C:29]([CH:31]=O)=[CH:30][C:25]=2[O:24][CH2:23][CH2:22]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>O1CCOCC1.CCOC(C)=O>[O:21]1[C:26]2[CH:27]=[CH:28][C:29]([CH2:31][NH:19][CH2:18][CH2:17][N:13]3[CH2:14][CH2:15][CH2:16][CH:12]3[C:10]3[CH:9]=[C:8]([CH3:20])[N:7]=[C:6]([N:1]4[CH:5]=[CH:4][N:3]=[CH:2]4)[N:11]=3)=[CH:30][C:25]=2[O:24][CH2:23][CH2:22]1

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 2481272,3-Dihydro-1,4-benzodioxin-6-carbaldehydeHCID 521998p-Toluenesulfonic acid monohydrateHCID 5049666Sodium triacetoxyborohydrideHCID 59551924HCID 59551924, compound

Product 1

HCID 59551907(2,3-Dihydro-benzo[1,4]dioxin-6-ylmethyl)-{2-[2-(2-imidazol-1-yl-6-methyl-pyrimidin-4-yl)-pyrrolidin-1-yl]-ethyl}-amineYield 57.4%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 2-[2-(2-imidazol-1-yl-6-methyl-pyrimidin-4-yl)-pyrrolidin-1-yl]-ethylamine (77 mg, 286 μmol), 2,3-dihydro-benzo[1,4]dioxine-6-carbaldehyde (47 mg, 286 μmol) and p-toluenesulfonic acid monohydrate (5 mg, 26 μmol) in dioxane (3 mL) was heated at 60° C. for 16 h. Sodium triacetoxyborohydride (180 mg, 860 μmol) was then added. The reaction mixture was stirred at r.t. for 1 h. EtOAc (25 mL) and 1N NaOH (25 mL) were then added. The organic layer was isolated, dried (MgSO4), filtered, and concentrated. Silica gel chromatography (0% to 10% MeOH/DCM) afforded 69 mg (57%) of (2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-{2-[2-(2-imidazol-1-yl-6-methyl-pyrimidin-4-yl)-pyrrolidin-1-yl]-ethyl}-amine. [M+H]+ 421.23; 1H NMR (400 MHz, CDCl3) δ 8.60 (s, 1H), 7.89 (s, 1H), 7.23 (s, 1H), 7.12 (s, 1H), 6.68-6.79 (m, 3H), 4.21 (s, 4H), 3.54 (t, 1H), 3.22 (m, 1H), 2.70-2.82 (m, 2H), 2.20-2.60 (m, 9H), 1.84 (m, 2H), 1.70 (m, 1H).

Workup

  1. customThe organic layer was isolated
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-6ffd52453dc8419c802fb4885016908d
Source dataset
uspto-grants-2010_11
Patent number
US07825256B2

Reaction notes

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