1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 44511937, Verbindung

HRID 1782575Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1782575
[NH2:1][CH2:2][CH2:3][C@H:4]([N:6]1[CH2:11][CH2:10][CH:9]([N:12]([CH2:23][C:24]2[CH:25]=[N:26][CH:27]=[CH:28][C:29]=2[CH3:30])[C:13]2[CH:14]=[N:15][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:18]=2)[CH2:8][CH2:7]1)[CH3:5].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.Cl.[Cl:53][C:54]1[CH:62]=[C:61]([CH3:63])[C:57]([C:58](O)=[O:59])=[C:56]([CH3:64])[N:55]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:53][C:54]1[CH:62]=[C:61]([CH3:63])[C:57]([C:58]([NH:1][CH2:2][CH2:3][C@H:4]([N:6]2[CH2:11][CH2:10][CH:9]([N:12]([CH2:23][C:24]3[CH:25]=[N:26][CH:27]=[CH:28][C:29]=3[CH3:30])[C:13]3[CH:14]=[N:15][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:18]=3)[CH2:8][CH2:7]2)[CH3:5])=[O:59])=[C:56]([CH3:64])[N:55]=1

Komponenten

7

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 68971363HCID 68971363, VerbindungHCID 717213646-Chloro-2,4-dimethylpyridine-3-carboxylic acid--hydrogen chloride (1/1)

Produkt 1

HCID 44511937HCID 44511937, VerbindungAusbeute 61 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

[1-((R)-3-Amino-1-methyl-propyl)-piperidin-4-yl]-(4-methyl-pyridin-3-ylmethyl)-(6-trifluoromethyl-pyridin-3-yl)-amine (72.9 mg, 0.17 mmol), EDCI (36.4 mg, 0.19 mmol) and HOBT (25.7 mg, 0.19 mmol) were combined in DMF (5 mL) to give a pale yellow solution. To this solution was added 6-chloro-2,4-dimethyl-nicotinic acid hydrochloride salt (42.2 mg, 0.19 mmol) followed by DIPEA (66.3 μL, 0.38 mmol) and the resulting mixture was stirred at room temperature for 16 h. Standard workup according to General Procedure C gave the crude product as a tan oil. Purification by preparative TLC (91:8:1, CH2Cl2/MeOH/NH4OH) afforded 6-chloro-2,4-dimethyl-N-((R)-3-{4-[(4-methyl-pyridin-3-ylmethyl)-(6-trifluoromethyl-pyridin-3-yl)-amino]-piperidin-1-yl}-butyl)-nicotinamide as a white foam (61.1 mg, 60%). 1H NMR (CDCl3) δ 1.03 (d, 3H, J=5 Hz), 1.23 (m, 1H), 1.40 (m, 1H), 1.65 (m, 3H), 1.76 (m, 1H), 1.91 (d, 2H, J=11 Hz), 2.24 (m, 1H), 2.30 (s, 3H), 2.41 (s, 3H), 2.51 (s, 3H), 2.61 (m, 1H), 2.85 (m, 3H), 3.40 (m 1H), 3.48 (s, 1H), 3.74 (m, 2H), 4.25 (s, 2H), 6.84 (dd, 1H, J=3 Hz, 9 Hz), 6.99 (s, 1H), 7.13 (d, 1H, J=5 Hz), 7.41 (m, 2H), 8.05 (d, 1H, J=3 Hz), 8.17 (s, 1H), 8.38 (d, 1H, J=5 Hz). ES-MS m/z 589 (M+H), 612 (M+Na). Anal. Calcd. For C30H36ClF3N6O: C, 61.17; H, 6.16; Cl, 6.02; F, 9.67; N, 14.27.

Aufarbeitung

  1. customto give a pale yellow solution
  2. customgave the crude product as a tan oil
  3. customPurification by preparative TLC (91:8:1, CH2Cl2/MeOH/NH4OH)

Quellen und Nachweise

ORD-Eintrag
ord-bf83bf337f5742bfbdeac286f7db7407
Quelldatensatz
uspto-grants-2009_03
Patentnummer
US07498346B2

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