Nitrogen → HCID 16049103, compound

HRID 1916358Notes

Reaction equation

HRID 1916358 reaction equation
Br[C:2]1[S:10][C:9]2[C:8](=[O:11])[N:7]([C:12]3[CH:23]=[CH:22][C:15]([O:16][CH2:17][C:18]([CH3:21])([OH:20])[CH3:19])=[C:14]([O:24][CH3:25])[CH:13]=3)[CH:6]=[N:5][C:4]=2[CH:3]=1.[Cl:26][C:27]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+].N#N>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>[Cl:26][C:27]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=1[C:2]1[S:10][C:9]2[C:8](=[O:11])[N:7]([C:12]3[CH:23]=[CH:22][C:15]([O:16][CH2:17][C:18]([CH3:21])([OH:20])[CH3:19])=[C:14]([O:24][CH3:25])[CH:13]=3)[CH:6]=[N:5][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 2734659(2,4-Dichlorophenyl)boronic acidHCID 58858091HCID 58858091, compound

Product 1

HCID 16049103HCID 16049103, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
110 °C

Procedure

A mixture of 1-(4-(6-bromo-4-oxo-thieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)-2-methyl-2-propanol (50 mg, 0.12 mmol), 2,4-dichlorobenzeneboronic acid (21 mg, 0.18 mmol), Na2CO3 (31 mg, 0.29 mmol), tetrakis(triphenylphosphine)palladium (10 mg, 0.0088 mmol), N2-degassed dioxane (1 mL) and N2-degassed water (0.5 mL) was heated in a 110° C. bath for 30 min. The mixture, upon cooling, was poured into half-saturated NaHCO3 (3 mL). The mixture was extracted with CH2Cl2 (2×5 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. The residue was chromatographed (4 g silica, CH2Cl2 to 50% EtOAc-CH2Cl2) to provide 1-(4-(6-(2,4-dichlorophenyl)-4-oxo-thieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)-2-methyl-2-propanol as an off-white solid (41 mg, 71%). 1H-NMR (CDCl3) δ 8.09 (s, 1 H), 7.54 (s, 1 H), 7.49 (m, 2 H), 7.29 (dd, J=8, 2 Hz, 1 H), 6.84-6.96 (m, 3 H), 3.81 (s, 5 H), 1.30 (s, 6H); HPLC (Method #7) 4.2 min; LCMS (ES) m/z 491 (M+H).

Workup

  1. customdegassed dioxane (1 mL) and N2-
  2. customdegassed water (0.5 mL)
  3. temperatureThe mixture, upon cooling
  4. additionwas poured into half-saturated NaHCO3 (3 mL)
  5. extractionThe mixture was extracted with CH2Cl2 (2×5 mL)
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue was chromatographed (4 g silica, CH2Cl2 to 50% EtOAc-CH2Cl2)

Sources & evidence

ORD record
ord-ca131da005024d13aec9f0459ec16b37
Source dataset
uspto-grants-2013_12
Patent number
US08618115B2

Reaction notes

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