Phenethylamine → HCID 86703983, compound

HRID 1773904Notes

Reaction equation

HRID 1773904 reaction equation
I[C:2]1[N:11]=[C:10]2[N:4]([CH2:5][CH2:6][C:7]3[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=3[CH:9]2[O:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[C:3]=1[CH3:24].[CH2:25]([CH2:32][NH2:33])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.N12CCCN=C1CCCCC2.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.[O:63]1CCC[CH2:64]1>C(OCC)(=O)C.[OH-].[Na+].CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC(O)=O.CC(O)=O.[Pd].[Pd].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo]>[CH2:25]([CH2:32][NH:33][C:64]([C:2]1[N:11]=[C:10]2[N:4]([CH2:5][CH2:6][C:7]3[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=3[CH:9]2[O:12][CH:13]2[CH2:14][CH2:15][N:16]([CH3:19])[CH2:17][CH2:18]2)[C:3]=1[CH3:24])=[O:63])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

10

Reactant 5

HCID 1001PhenethylamineHCID 8028TetrahydrofuranHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 86703973HCID 86703973, compound

Product 1

HCID 86703983HCID 86703983, compound

Reagents, catalysts & solvents 4

HCID 98885Molybdenum carbonyl (Mo(CO)6)CatalystHCID 11104995trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)CatalystHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 2-iodo-1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 133) (80 mg, 0.18 mmole), N-benzylmethylamine (42 μL, 0.32 mmole), 1,8-diazabicyclo(5.4.0)undec-7-ene (24 μL, 0.16 mmole), trans-di-μ-acetatobis[2-(di-o-tolyl-phosphino)-benzyl]dipalladium(II) (11.5 mg), tri-tertbutylphosphonium tetrafluoroborate (8.5 mg) and molybdenum hexacarbonyl (30 mg, 0, 11 mmole) in tetrahydrofuran (1.5 mL) are introduced in a screw-capped vial. The vial is stirred at 130° C. for 1.5 hours, then cooled to room temperature, diluted with ethyl acetate and 1N aqueous sodium hydroxide. The organic phase is dried over magnesium sulphate and concentrated under reduced pressure. The residue is purified by preparative HPLC-MS (Waters AutoPurification HPLC/MS System, Sunfire Prep C18 5 μm OBD 30×150 mm column, eluents: water/0.1% formic acid (A) and acetonitrile/0.1% formic acid (B), focus gradient from 21% (B) to 31% (B) in 10 minutes) to afford pure 1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene-2-carboxylic acid benzylmethylamide melting at 61° C.

Workup

  1. additionare introduced in a screw-capped vial
  2. temperaturecooled to room temperature
  3. dry with materialThe organic phase is dried over magnesium sulphate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue is purified by preparative HPLC-MS (Waters AutoPurification HPLC/MS System, Sunfire Prep C18 5 μm OBD 30×150 mm column, eluents: water/0.1% formic acid (A) and acetonitrile/0.1% formic acid (B), focus gradient from 21% (B) to 31% (B) in 10 minutes)

Sources & evidence

ORD record
ord-305ba2529b7045b0977949fcb374d6d3
Source dataset
uspto-grants-2016_02
Patent number
US09255101B2

Reaction notes

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