Phenethylamine → HCID 86703983、化合物

HRID 1773904ノート

反応式

HRID 1773904 の反応式
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

参加物

10

反応物 5

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

生成物 1

HCID 86703983HCID 86703983、化合物

試薬・触媒・溶媒 4

HCID 98885Molybdenum carbonyl (Mo(CO)6)触媒HCID 11104995trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)触媒HCID 8857Ethyl Acetate溶媒HCID 14798Sodium Hydroxide溶媒

反応条件

温度
130 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-305ba2529b7045b0977949fcb374d6d3
出典データセット
uspto-grants-2016_02
特許番号
US09255101B2

反応ノート

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