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

HRID 1770978Notes

Reaction equation

HRID 1770978 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 ethynylcyclopropane (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): 1H NMR (500 MHz, DMSO-d6) δ ppm 0.60-0.73 (m, 2H), 0.77-0.89 (m, 2H), 1.46 (tt, 1H), 1.50-1.65 (m, 4H), 1.72-1.85 (m, 1H), 2.08-2.16 (m, 1H), 2.18 (s, 3H), 3.07-3.23 (m, 2H), 6.54 (d, 1H), 6.60 (s, 2H), 7.16 (dd, 1H), 7.20-7.27 (m, 1H); 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-8d31e27849df4d1fa89a0e59b852c89b
Source dataset
uspto-grants-2016_02
Patent number
US09248129B2

Reaction notes

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