1,2-Dichloroethane → N-(2-hydroxy-2-methylpropyl)-4-(4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridin-1(2H)-ylsulfonyl)butanamide

HRID 1429575Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1429575
[CH2:1]([C:4]1[CH:5]=[N:6][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([O:16][C:17]3[S:18][C:19]4[CH:25]=[C:24]([C:26]5[CH2:31][CH2:30][N:29]([S:32]([CH2:35][CH2:36][CH2:37][C:38](O)=[O:39])(=[O:34])=[O:33])[CH2:28][CH:27]=5)[CH:23]=[CH:22][C:20]=4[N:21]=3)[CH2:12][CH2:11]2)=[N:8][CH:9]=1)[CH2:2][CH3:3].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[NH2:55][CH2:56][C:57]([CH3:60])([OH:59])[CH3:58].CCN(CC)CC>C(Cl)Cl>[OH:59][C:57]([CH3:60])([CH3:58])[CH2:56][NH:55][C:38](=[O:39])[CH2:37][CH2:36][CH2:35][S:32]([N:29]1[CH2:30][CH2:31][C:26]([C:24]2[CH:23]=[CH:22][C:20]3[N:21]=[C:17]([O:16][CH:13]4[CH2:12][CH2:11][N:10]([C:7]5[N:6]=[CH:5][C:4]([CH2:1][CH2:2][CH3:3])=[CH:9][N:8]=5)[CH2:15][CH2:14]4)[S:18][C:19]=3[CH:25]=2)=[CH:27][CH2:28]1)(=[O:34])=[O:33]

Komponenten

7

Edukt 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 951022-Propanol, 1-amino-2-methyl-HCID 674656774-(4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridin-1(2H)-ylsulfonyl)butanoic acid

Produkt 1

HCID 71270070N-(2-hydroxy-2-methylpropyl)-4-(4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridin-1(2H)-ylsulfonyl)butanamideAusbeute 68,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a solution of 4-(4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridin-1(2H)-ylsulfonyl)butanoic acid (30 mg, 0.051 mmol), HOBT (10.2 mg, 0.067 mmol), and EDC (12.8 mg, 0.067 mmol) in CH2Cl2 (1 mL) was added 1-amino-2-methylpropan-2-ol (6.9 mg, 0.077 mmol) followed by slow addition of Et3N (0.03 mL, 0.205 mmol). The reaction mixture was stirred at rt overnight. The reaction mixture was diluted with CH2Cl2 (2 mL), washed with water (2 mL), then brine. The organic layer was dried (Na2SO4), filtered, and concentrated. The residue was recrystallized from 10% water in CH3CN to afford N-(2-hydroxy-2-methylpropyl)-4-(4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridin-1(2H)-ylsulfonyl)butanamide (24 mg, 0.035 mmol, 68% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ 8.17 (s, 2H), 7.63 (d, J=2.2 Hz, 1H), 7.62 (d, J=4.1 Hz, 1H), 7.38 (dd, J=8.5, 1.7 Hz, 1H), 6.06 (dt, J=3.2, 1.8 Hz, 1H), 6.04-5.99 (m, 1H), 5.45 (tt, J=7.9, 3.8 Hz, 1H), 4.22 (ddd, J=13.3, 6.9, 4.0 Hz, 2H), 4.02 (q, J=2.6 Hz, 2H), 3.73-3.62 (m, 2H), 3.57 (t, J=5.6 Hz, 2H), 3.28 (d, J=6.1 Hz, 2H), 3.10 (t, J=7.0 Hz, 2H), 2.70-2.64 (m, 2H), 2.49 (t, J=6.7 Hz, 2H), 2.41 (t, J=7.4 Hz, 2H), 2.26-2.14 (m, 5H), 1.94 (dtd, J=12.8, 8.3, 3.9 Hz, 2H), 1.62-1.55 (m, 2H), 1.23 (s, 6H), 0.94 (t, J=7.3 Hz, 3H). LCMS (m/z)=657 (M+H)+.

Aufarbeitung

  1. washwashed with water (2 mL)
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was recrystallized from 10% water in CH3CN

Quellen und Nachweise

ORD-Eintrag
ord-d870c29b8c724e8f9fc90abd57a4ac02
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08940716B2

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