Phenethylamine → HCID 86703983, 화합물

HRID 1773904노트

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HRID 1773904 반응식
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

참가 물질

10

반응물 5

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

생성물 1

HCID 86703983HCID 86703983, 화합물

시약·촉매·용매 4

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

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온도
130 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-305ba2529b7045b0977949fcb374d6d3
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09255101B2

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