Methanol → N-Cyclohexyl-N-(2,2-dimethoxyethyl)-3-(3-(1-methyl-1H-pyrazol-4-yl)phenethoxy)propanamide

HRID 909882Notes

Reaction equation

HRID 909882 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][CH:27]=1)[CH2:5][CH2:6][O:7][CH2:8][CH2:9][C:10]([N:12]([CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1)[CH2:13][CH:14]([O:17][CH3:18])[O:15][CH3:16])=[O:11].[CH3:28][N:29]1[CH:33]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH:31]=[N:30]1.C(=O)([O-])[O-].[K+].[K+].CO>C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:19]1([N:12]([CH2:13][CH:14]([O:17][CH3:18])[O:15][CH3:16])[C:10](=[O:11])[CH2:9][CH2:8][O:7][CH2:6][CH2:5][C:4]2[CH:25]=[CH:26][CH:27]=[C:2]([C:32]3[CH:31]=[N:30][N:29]([CH3:28])[CH:33]=3)[CH:3]=2)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1

Participants

7

Reactant 4

HCID 887MethanolHCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 592904803-(3-Bromophenethoxy)-N-cyclohexyl-N-(2,2-dimethoxyethyl)propanamide

Product 1

HCID 59290438N-Cyclohexyl-N-(2,2-dimethoxyethyl)-3-(3-(1-methyl-1H-pyrazol-4-yl)phenethoxy)propanamideYield 108.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

To 3-(3-bromophenethoxy)-N-cyclohexyl-N-(2,2-dimethoxyethyl)propanamide (1.4 g), prepared as in Preparation 3 Step iii), within a 35 mL microwave tube with stirrer were added 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.92 g), potassium carbonate (0.88 g) and Pd(Ph3P)4 (0.18 g) followed by methanol (8 mL). The vial was sealed and heated within a CEM Discover microwave at 100° C. for 15 min. The mixture was diluted with DCM and washed once with water, once with brine, dried over sodium sulphate and the solvent evaporated to afford crude material as an orange oil. This was purified on silica using ethyl acetate as the eluent to afford the product (1.52 g). MS [M+H-MeOH]+=412 (MultiMode+) 1H NMR (400 MHz, CD3OD) δ 7.92 (s, 1H), 7.78 and 7.77 (2×s, 1H), 7.40-7.32 (m, 2H), 7.23 and 7.22 (2×t, J=7.6 Hz, 1H), 7.07-7.03 (m, 1H), 4.52 and 4.36 (2×t, J=5.3 Hz, 1H), 4.05-3.95 and 3.69-3.60 (2×m, 1H), 3.901 and 3.898 (2×s, 3H), 3.75-3.64 (m, 4H), 3.34 (s, 3H), 3.32 (s, 3H), 3.34 and 3.25 (2×d, J=5.1 Hz, 2H), 2.84 and 2.83 (2×t, J=6.6 Hz, 2H), 2.65 and 2.63 (2×t, J=6.1 Hz, 2H), 1.79-1.04 (m, 10H); a ˜1:1 mixture of rotamers is observed.

Workup

  1. customThe vial was sealed
  2. washwashed once with water, once with brine
  3. dry with materialdried over sodium sulphate
  4. customthe solvent evaporated
  5. customto afford crude material as an orange oil
  6. customThis was purified on silica

Sources & evidence

ORD record
ord-f8dc062c5dc941839f436731d63263d2
Source dataset
uspto-grants-2011_09
Patent number
US08017602B2

Reaction notes

Loading…