Ethylurea → HCID 71623037, compound

HRID 2174246Notes

Reaction equation

HRID 2174246 reaction equation
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:19]=[CH:18][C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][CH:10]=2)[C:5]([C:20](=[O:28])[NH:21][C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)=[CH:4][N:3]=1.[CH2:29]([NH:31][C:32]([NH2:34])=[O:33])[CH3:30].CC(C)([O-])C.[Na+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1>[CH2:29]([NH:31][C:32](=[O:33])[NH:34][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:19]=[CH:18][C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][CH:10]=2)[C:5]([C:20](=[O:28])[NH:21][C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)=[CH:4][N:3]=1)[CH3:30]

Participants

6

Reactant 4

HCID 12254EthylureaHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 89650662HCID 89650662, compound

Product 1

HCID 71623037HCID 71623037, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

Compound ii (210 mg, 0.53 mmol) and N-ethylurea (93 mg, 1.1 mmol) were dissolved in degassed dioxane (2 mL) under an atmosphere of nitrogen. Sodium tert-butoxide (102 mg, 1.1 mmol), X-phos (2-(Dicyclohexylphosphino)-2′,4′,6′-tri-1-propyl-1,1′-biphenyl, 50 mg, 0.1 mmol) and palladium(0)bis(dibenzylideneacetone) (50 mg, 0.05 mmol) were added sequentially. The mixture was heated at 120° C. in a microwave reactor for 60 min. The mixture was cooled to RT, filtered then evaporated to dryness. The residue was purified by flash chromatography (40 g GraceResolv silica cartridge, 0-15% MeOH in DCM) to yield Compound 15 as an off white solid (160 mg, 68%). 1H NMR (400 MHz, DMSO-d6): δ 10.53 (s, 1H), 10.06 (s, 1H), 9.24 (s, 1H), 8.86 (s, 1H), 8.64 (s, 1H), 8.32 (d, J=4.8 Hz, 1H), 8.12 (d, J=7.6 Hz, 1H), 7.95 (d, J=8.4 Hz, 2H), 7.80 (m, 1H), 7.55 (s, 1H), 7.40 (d, J=8.8 Hz, 311), 4.32-4.27 (m, 2H), 3.17-3.14 (m, 2H), 1.34 (t, J=7.2 Hz, 3H), 1.12-1.09 (m, 3H). [M+H]+ m/z=449.16.

Workup

  1. temperatureThe mixture was cooled to RT
  2. filtrationfiltered
  3. customthen evaporated to dryness
  4. customThe residue was purified by flash chromatography (40 g GraceResolv silica cartridge, 0-15% MeOH in DCM)

Sources & evidence

ORD record
ord-28da176137e7495b9ef38b3c9f11b667
Source dataset
uspto-grants-2015_06
Patent number
US09060515B2

Reaction notes

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