Cesium carbonate → HCID 59708435, compound

HRID 1641363Notes

Reaction equation

HRID 1641363 reaction equation
[O:1]=[S:2]1[C:10]2[C:9]([NH:11][CH2:12][CH2:13][CH3:14])=[N:8][C:7]([N:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)=[N:6][C:5]=2[CH2:4][CH2:3]1.Br[C:22]1[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][CH:23]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[O:1]=[S:2]1[C:10]2[C:9]([NH:11][CH2:12][CH2:13][CH3:14])=[N:8][C:7]([N:15]3[CH2:20][CH2:19][N:18]([C:22]4[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][CH:23]=4)[CH2:17][CH2:16]3)=[N:6][C:5]=2[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 12162Benzonitrile, 4-bromo-HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59708496HCID 59708496, compound

Product 1

HCID 59708435HCID 59708435, compoundYield 52.8%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

Under an argon atmosphere 400 mg (5-oxo-2-piperazin-1-yl-6,7-dihydro-5H-5λ4-thieno[3,2-d]pyrimidin-4-yl)-propylamine (prepared in a similar manner to that described in Example 32), 245 mg 4-bromobenzonitrile, 321 mg palladium(II)acetate, 120 mg Xantphos and 620 mg caesium carbonate are stirred in 2.50 ml degassed toluene for 5 hours at 80° C. After cooling the reaction mixture is extracted with ethyl acetate and saturated sodium chloride solution. The organic phase is dried and evaporated to dryness. The residue is purified by preparative HPLC (method A). 282 mg of the product are obtained as a powder. Analytical HPLC-MS (method A): RT=2.37 min The two enantiomers may be separated by chiral HPLC (column: Diacel OD-H, 250×4.6 mm, 5 μm, eluant: (hexane+cyclohexylamine (0.2%))/EtOH (65/35), flow rate: 1 ml/min): enantiomer 1: RT=7.9 min (Example 148); enantiomer 2: RT=9.6 min.

Workup

  1. customdegassed toluene for 5 hours at 80° C
  2. temperatureAfter cooling the reaction mixture
  3. extractionis extracted with ethyl acetate and saturated sodium chloride solution
  4. customThe organic phase is dried
  5. customevaporated to dryness
  6. customThe residue is purified by preparative HPLC (method A)

Sources & evidence

ORD record
ord-191feff8482d43fb9b0cb3f7d12b5dc7
Source dataset
uspto-grants-2012_02
Patent number
US08114878B2

Reaction notes

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