Ethanol → HCID 178453511, compound

HRID 717744Notes

Reaction equation

HRID 717744 reaction equation
[C:1]([O:5][C:6](=[O:35])[N:7]([CH2:24][CH2:25][CH2:26][NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:8][C:9]1[CH:14]=[CH:13][C:12](B2OC(C)(C)C(C)(C)O2)=[CH:11][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].I[C:37]1[C:38](=[O:50])[N:39]=[C:40]2[NH:45][C:44]3[CH:46]=[CH:47][CH:48]=[CH:49][C:43]=3[N:41]2[CH:42]=1.C(O)C.O1CCOCC1>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.O>[C:1]([O:5][C:6](=[O:35])[N:7]([CH2:24][CH2:25][CH2:26][NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:8][C:9]1[CH:10]=[CH:11][C:12]([C:37]2[C:38](=[O:50])[N:39]=[C:40]3[NH:45][C:44]4[CH:46]=[CH:47][CH:48]=[CH:49][C:43]=4[N:41]3[CH:42]=2)=[CH:13][CH:14]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 4

HCID 702EthanolHCID 312751,4-DioxaneHCID 66578953(3-Tert-butoxycarbonylamino-propyl)-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl]-carbamic acid tert-butyl esterHCID 178517390HCID 178517390, compound

Product 1

HCID 178453511HCID 178453511, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 2-iodo-3-methoxy-acrylic acid methyl ester (1, 1.21 g, 5 mmol), 1H-benzoimidazol-2-ylamine (2, 0.67 g, 5 mmol) and ethanol (30 mL) was added a solution of sodium methoxide (10 mL, 0.5 M in methanol, 5 mmol). The resulted mixture was refluxed for 3 h and concentrated to afford 3-iodo-10H-benzo[4,5]imidazo[1,2-a]pyrimidin-2-one (3). A mixture of (3-tert-butoxycarbonylamino-propyl)-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl]carbamic acid tert-butyl ester (4, 490 mg, 1 mmol), 3 (311 mg, 1 mmol), K2CO2 (414 g, 3 mmol), Pd(PPh3)4 (0) (41 mg, 0.05 mmol), ethanol (6 mL), dioxane (2 mL) and water (2 mL) was degassed and heated at 80° C. for 20 h under argon atmosphere. The reaction mixture was diluted with EtOAc (500 mL), washed with water (300 mL) and brine (300 mL). The organic solution was concentrated and purified by flash chromatography (0%-6% MeOH in methanechloride) to give desired product 5 (170 mg, 31%) as light yellow solid. LCMS (EI) m/z: 570 (M+Na+).

Workup

  1. customwas degassed
  2. additionThe reaction mixture was diluted with EtOAc (500 mL)
  3. washwashed with water (300 mL) and brine (300 mL)
  4. concentrationThe organic solution was concentrated
  5. custompurified by flash chromatography (0%-6% MeOH in methanechloride)

Sources & evidence

ORD record
ord-25c77b7106e148ffa9c7a87047b666de
Source dataset
uspto-grants-2015_11
Patent number
US09193731B2

Reaction notes

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