Triethylamine → 6'-(Cyclopropylethynyl)-5''-methyl-3'H-dispiro[cyclobutane-1, 2'-indene-1',2''-imidazol]-4''-amine

HRID 539376Notes

Reaction equation

HRID 539376 reaction equation
Br[C:2]1[CH:19]=[C:18]2[C:5]([CH2:6][C:7]3([C:11]42[N:15]=[C:14]([NH2:16])[C:13]([CH3:17])=[N:12]4)[CH2:10][CH2:9][CH2:8]3)=[CH:4][CH:3]=1.[C:20]([CH:22]1[CH2:24][CH2:23]1)#[CH:21].C(N(CC)CC)C>CN(C=O)C.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:22]1([C:20]#[C:21][C:2]2[CH:19]=[C:18]3[C:5]([CH2:6][C:7]4([C:11]53[N:15]=[C:14]([NH2:16])[C:13]([CH3:17])=[N:12]5)[CH2:8][CH2:9][CH2:10]4)=[CH:4][CH:3]=2)[CH2:24][CH2:23]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 138823CyclopropylacetyleneHCID 573866666'-Bromo-5''-methyl-3'H-dispiro[cyclobutane-1,2'-indene-1',2''-imidazol]-4''-amine

Product 1

HCID 573866696'-(Cyclopropylethynyl)-5''-methyl-3'H-dispiro[cyclobutane-1, 2'-indene-1',2''-imidazol]-4''-amineYield 48.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 6′-bromo-5″-methyl-3′H-dispiro[cyclobutane-1,2′-indene-1′,2″-imidazol]-4″-amine (Example 54, 0.10 g, 0.31 mmol) in DMF (10 mL) under argon was added ethynylcyclo-propane (0.031 g, 0.47 mmol), tetrakis(triphenylphosphine)palladium(0) (0.036 g, 0.03 mmol) and triethylamine (1.31 mL, 9.43 mmol). The reaction mixture was stirred at r.t. for 5 min before addition of cuprous iodide (8.98 mg, 0.05 mmol). The reaction mixture was stirred overnight at 65° C. The reaction mixture was partitioned between sat aq. NaHCO3 and EtOAc. The organic phase was dried over MgSO4 and concentrated to give a crude product which was purified by preparative chromatography to afford the title compound (0.046 g, 48% yield): 1 H NMR (500 MHz, DMSO-d6) δ ppm 0.60-0.73 (m, 2 H), 0.77-0.89 (m, 2 H), 1.46 (tt, 1 H), 1.50-1.65 (m, 4 H), 1.72-1.85 (m, 1 H), 2.08-2.16 (m, 1 H), 2.18 (s, 3 H), 3.07-3.23 (m, 2 H), 6.54 (d, 1 H), 6.60 (s, 2 H), 7.16 (dd, 1 H), 7.20-7.27 (m, 1 H); MS (ES+) m/z 304 [M+H]+.

Workup

  1. customThe reaction mixture was partitioned
  2. dry with materialThe organic phase was dried over MgSO4
  3. concentrationconcentrated
  4. customto give a crude product which
  5. customwas purified by preparative chromatography

Sources & evidence

ORD record
ord-eb26b8cdc06b4d5a8efe174bbace31d0
Source dataset
uspto-grants-2014_10
Patent number
US08865911B2

Reaction notes

Loading…