Diisopropylethylamine → N1-((1S,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((R)-morpholin-3-yl)propan-2-yl)-N3,N3-dipropylisophthalamide

HRID 20957

Reaktionsgleichung

Reaktionsgleichung von HRID 20957
[CH2:1]([O:4][C@H:5]1[CH2:9][N:8](C(C2C=CC=CC=2)C2C=CC=CC=2)[C@@H:7]([C@@H:23]([OH:52])[C@@H:24]([NH:34][C:35](=[O:51])[C:36]2[CH:50]=[CH:49][CH:48]=[C:38]([C:39]([N:41]([CH2:45][CH2:46][CH3:47])[CH2:42][CH2:43][CH3:44])=[O:40])[CH:37]=2)[CH2:25][C:26]2[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([F:33])[CH:27]=2)C1)C=C.C(N1CCOC[C@@H]1[C@@H](O)[C@@H](NC(=O)C1C=CC=C(C(N(CCC)CCC)=O)C=1)CC1C=C(F)C=C(F)C=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(N(CCC)C(C1C=C(C=CC=1)C(O)=O)=O)CC.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.N[C@@H](CC1C=C(F)C=C(F)C=1)[C@@H]([C@H]1COCCN1C(C1C=CC=CC=1)C1C=CC=CC=1)O>ClCCl>[F:33][C:28]1[CH:27]=[C:26]([CH2:25][C@H:24]([NH:34][C:35](=[O:51])[C:36]2[CH:50]=[CH:49][CH:48]=[C:38]([C:39]([N:41]([CH2:45][CH2:46][CH3:47])[CH2:42][CH2:43][CH3:44])=[O:40])[CH:37]=2)[C@H:23]([OH:52])[C@H:7]2[CH2:1][O:4][CH2:5][CH2:9][NH:8]2)[CH:31]=[C:30]([F:32])[CH:29]=1

Komponenten

8

Edukt 6

HCID 81531DiisopropylethylamineHCID 1827693-(Dipropylcarbamoyl)benzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59733914(1S,2S)-2-Amino-1-((R)-4-benzhydrylmorpholin-3-yl)-3-(3,5-difluorophenyl)propan-1-olHCID 68497146N1-((1S,2S)-1-((R)-4-benzhydrylmorpholin-3-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-N3,N3-dipropylisophthalamideHCID 68497616N1-((1S,2S)-1-((2R,4R)-4-(allyloxy)-1-benzhydrylpyrrolidin-2-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-N3,N3-dipropylisophthalamide

Produkt 1

HCID 11848527N1-((1S,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((R)-morpholin-3-yl)propan-2-yl)-N3,N3-dipropylisophthalamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

Step 5 (A): N1-((1S,2S)-1-((R)-4-benzhydrylmorpholin-3-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-N3,N3-dipropylisophthalamide. To a solution of 3-(dipropylcarbamoyl)benzoic acid (Preparation E, 14 mg, 0.055 mmol) in dichloromethane (1 mL) was added Hunig's base (18 mg, 0.14 mmol) to make a clear solution and HATU (25 mg, 0.064 mmol) was then added. After stirring for 20 min, the reaction mixture was added (1S,2S)-2-amino-1-((R)-4-benzhydrylmorpholin-3-yl)-3-(3,5-difluorophenyl)propan-1-ol (Preparation D, (20 mg, 0.046 mmol) and the reaction mixture was stirred at rt overnight. Dichloromethane (100 mL) was added and washed with H2O (50 mL) twice, dried over Na2SO4, and concentrated to give the title compound as a crude product ready for next step without purification: 1H NMR (CD3OD, 500 MHz) δ 0.71 (3H, m), 1.01 (3H, m), 1.52 (2H, m), 1.74 (2H, m), 2.52 (1H, d, J=5 Hz), 2.63 (2H, dd, J=5, 15 Hz), 2.71 (1H, m), 3.12-3.19 (3H, m), 3.44-3.49 (3H, m), 3.94-3.99 (2H, m),4.04 (1H, m), 4.58 (1H, m), 5.06 (1H, m), 5.50 (1H, s), 6.76 (1H, m), 6.92-6.95 (2H, m), 7.14-7.19 (3H, m), 7.25-7.32 (3H, m), 7.44 (2H, m), 7.49-7.55 (2H, m), 7.58 (2H, d, J=10 Hz), 7.63 (1H, s), 7.73-7.76 (1H, m).

Aufarbeitung

  1. additionwas then added
  2. customPreparation D, (20 mg, 0.046 mmol)
  3. stirringthe reaction mixture was stirred at rt overnight
  4. washwashed with H2O (50 mL) twice
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-b077e03fb39a4f5c879440f20aeb9e9a
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07745470B2

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