Potassium Carbonate → (3S)-N,N-dibenzyl-5-(2-ethylpyrimidin-5-yl)chroman-3-amine

HRID 1099410Notes

Reaction equation

HRID 1099410 reaction equation
[CH2:1]([N:8]([CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C@H:9]1[CH2:18][C:17]2[C:12](=[CH:13][CH:14]=[CH:15][C:16]=2B2OC(C)(C)C(C)(C)O2)[O:11][CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:36]1[CH:37]=[N:38][C:39]([CH2:42][CH3:43])=[N:40][CH:41]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.CC(P(C(C)(C)C)C1[CH-]C=CC=1)(C)C.CC(P(C(C)(C)C)C1[CH-]C=CC=1)(C)C.[Cl-].[Cl-].[Fe+2].[Pd+2]>[CH2:28]([N:8]([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C@H:9]1[CH2:18][C:17]2[C:12](=[CH:13][CH:14]=[CH:15][C:16]=2[C:36]2[CH:37]=[N:38][C:39]([CH2:42][CH3:43])=[N:40][CH:41]=2)[O:11][CH2:10]1)[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 25114260(S)-N,N-dibenzyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)chroman-3-amineHCID 251500695-Bromo-2-ethylpyrimidine

Product 1

HCID 25115366(3S)-N,N-dibenzyl-5-(2-ethylpyrimidin-5-yl)chroman-3-amineYield 55%

Reagents, catalysts & solvents 2

HCID 53384307Dichloro[1,1'-bis(di-tert-butylphosphino)ferrocene]palladium(II)CatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of (3S)-N,N-dibenzyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)chroman -3-amine (278 mg, 0.61 mmol), 5-bromo-2-ethylpyrimidine (114 mg, 0.61 mmol), dichloro[1,1′bis(di-tert-butylphosphino)ferrocene]palladium(II) (24 mg, 0.04 mmol) and 2M potassium carbonate (0.64 mL, 1.28 mmol) in dioxane (6 mL) was irradiated in a microwave under an atmosphere of argon at 140° C. for 1 h. The reaction mixture was filtered through a pad of celite, which was washed with methanol, and the filtrate was concentrated in vacuo. The crude was partioned between ethyl acetate and water and the organic layer was dried and concentrated in vacuo. Purification by column chromatography, using a gradient of ethyl acetate in heptane gave 145 mg (55%) of the desired compound, 1H NMR (400 MHz, DMSO-d6) δ ppm 8.76 (s, 2 H), 7.23-7.35 (m, 8 H), 7.14-7.22 (m, 3 H), 6.78-6.87 (m, 2 H), 4.29-4.39 (m, 1 H), 4.04 (t, 1 H), 3.59-3.75 (m, 4 H), 3.03-3.14 (m, 1 H), 2.92-3.03 (m, 3 H), 2.52-2.57 (m, 1 H, obscured by DMSO), 1.36 (t, 3 H); MS (ESI) m/z 436[M+H+].

Workup

  1. customwas irradiated in a microwave under an atmosphere of argon at 140° C. for 1 h
  2. filtrationThe reaction mixture was filtered through a pad of celite, which
  3. washwas washed with methanol
  4. concentrationthe filtrate was concentrated in vacuo
  5. customthe organic layer was dried
  6. concentrationconcentrated in vacuo
  7. customPurification by column chromatography

Sources & evidence

ORD record
ord-30fce595a2e4432c88c536c2a79bb37c
Source dataset
uspto-grants-2012_03
Patent number
US08143408B2

Reaction notes

Loading…