Cesium carbonate → {4-[1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenyl}-carbamic acid tert-butyl ester

HRID 1773896Notes

Reaction equation

HRID 1773896 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:17]=[C:16]3[N:10]([CH2:11][CH2:12][C:13]4[CH:29]=[CH:28][CH:27]=[CH:26][C:14]=4[CH:15]3[O:18][CH:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)[C:9]=2[CH3:30])=[CH:4][CH:3]=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:79](=[O:86])([O:81][C:82]([CH3:85])([CH3:84])[CH3:83])[NH2:80]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].O1CCOCC1>[C:82]([O:81][C:79](=[O:86])[NH:80][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:17]=[C:16]3[N:10]([CH2:11][CH2:12][C:13]4[CH:29]=[CH:28][CH:27]=[CH:26][C:14]=4[CH:15]3[O:18][CH:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)[C:9]=2[CH3:30])=[CH:4][CH:3]=1)([CH3:85])([CH3:84])[CH3:83]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 726953822-(4-bromophenyl)-1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

Product 1

HCID 86703972{4-[1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenyl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

In a screw-capped vial are added 2-(4-bromophenyl)-1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 122A) (250 mg, 0.54 mmole), Pd(dba)2 (25 mg, 27 μmole), Xantphos (31 mg, 54 μmole), Cs2CO3 (704 mg, 2.16 mmoles), 1,4-dioxane (3.4 mL) and tert-butyl carbamate (316 mg, 2.7 mmoles). The flask is evacuated and filled with argon. The reaction mixture is heated at 110° C. for 4 hours. Water is added and pH adjusted to 10 with a few drops of 1N NaOH. The aqueous phase is extracted three times with CH2Cl2. The organic phase is dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is purified by silica gel chromatography using (CH2Cl2:MeOH:NH4OH) with a gradient from (100:0:0) to (95:5:0.5) to give {4-[1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenyl}-carbamic acid tert-butyl ester melting at 194° C.

Workup

  1. customThe flask is evacuated
  2. additionfilled with argon
  3. additionWater is added
  4. extractionThe aqueous phase is extracted three times with CH2Cl2
  5. dry with materialThe organic phase is dried over magnesium sulphate
  6. filtrationfiltered
  7. customthe solvent is removed under reduced pressure
  8. customThe residue is purified by silica gel chromatography

Sources & evidence

ORD record
ord-aa24120b1e1c40f682e7c6ac97e6d153
Source dataset
uspto-grants-2016_02
Patent number
US09255101B2

Reaction notes

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