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Cesium carbonate → HCID 57636053, compound

HRID 216258
Notes
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Reaction equation

HRID 216258 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([NH:10][CH2:11][CH:12]2[CH2:17][N:16]([CH3:18])[C:15]3[CH:19]=[CH:20][CH:21]=[CH:22][C:14]=3[O:13]2)[CH:3]=1.[C:23]([C:26]([C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1)([CH3:28])[CH3:27])([OH:25])=[O:24].C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC.O.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>[CH3:9][O:8][C:6]1[N:7]=[C:2]([C:31]2[CH:30]=[C:29]([C:26]([CH3:28])([CH3:27])[C:23]([OH:25])=[O:24])[CH:34]=[CH:33][CH:32]=2)[CH:3]=[C:4]([NH:10][CH2:11][CH:12]2[CH2:17][N:16]([CH3:18])[C:15]3[CH:19]=[CH:20][CH:21]=[CH:22][C:14]=3[O:13]2)[N:5]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 442489972-(3-Boronophenyl)-2-methylpropanoic acidHCID 86615713HCID 86615713, compound

Product 1

HCID 57636053HCID 57636053, compoundYield 68.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compound
Catalyst
HCID 962WaterSolvent2×
HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of (6-chloro-2-methoxy-pyrimidin-4-yl)-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-2-ylmethyl)-amine (200 mg, 0.62 mmol), 3-(1-carboxy-1-methyl-ethyl)-phenyl-boronic acid (190 mg, 0.94 mmol), and Cs2CO3 (0.51 g, 1.6 mmol) in ethylene glycol dimethyl ether (10 mL) and water (2 mL) is degassed by bubbling with Ar gas for 5 minutes, and treated with tetrakis(triphenylphosphine)palladium(0) (36 mg, 0.03 mmol) at room temperature. The mixture is heated at 85° C. for 6 h. The mixture is diluted with H2O (20 mL), and extracted with EtOAc (20 mL). The aqueous layer is separated, acidified to pH 3 with 1M HCl solution, and extracted with EtOAc (2×30 mL). The extracts are dried (MgSO4), filtered, and concentrated. The residue is chromatographed on SiO2 (70% EtOAc in heptane) to afford 2-(3-{2-methoxy-6-[(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-2-ylmethyl)-amino]-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid (190 mg, Example 92). LCMS: RT=2.59 minutes; MS: 449 (M+H). IC50=278 nM

Workup

  1. customis degassed
  2. customby bubbling with Ar gas for 5 minutes
  3. extractionextracted with EtOAc (20 mL)
  4. customThe aqueous layer is separated
  5. extractionextracted with EtOAc (2×30 mL)
  6. dry with materialThe extracts are dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue is chromatographed on SiO2 (70% EtOAc in heptane)

Sources & evidence

ORD record
ord-3ead01dbc94e4a86950eed2fba269354
Source dataset
uspto-grants-2012_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08193183B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes