Sodium triacetoxyborohydride → 4-((3,5-Dimethyl-pyridin-2-ylmethyl)-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-pyridin-2-ylmethyl}-amino)-piperidine-1-carboxylic acid tert-butyl ester

HRID 251170Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 251170
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][CH2:15][C:16]2[C:21]([C:22]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)([CH3:24])[CH3:23])=[CH:20][CH:19]=[CH:18][N:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:32][C:33]1[C:34]([CH:40]=O)=[N:35][CH:36]=[C:37]([CH3:39])[CH:38]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]([CH2:40][C:34]2[C:33]([CH3:32])=[CH:38][C:37]([CH3:39])=[CH:36][N:35]=2)[CH2:15][C:16]2[C:21]([C:22]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)([CH3:24])[CH3:23])=[CH:20][CH:19]=[CH:18][N:17]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Komponenten

5

Edukt 3

HCID 5049666Sodium triacetoxyborohydrideHCID 187316833,5-Dimethylpyridine-2-carbaldehydeHCID 672721454-({3-[1-(4-Fluoro-phenyl)-1-methyl-ethyl]-pyridin-2-ylmethyl}-amino)-piperidine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 672721664-((3,5-Dimethyl-pyridin-2-ylmethyl)-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-pyridin-2-ylmethyl}-amino)-piperidine-1-carboxylic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Using General Procedure B: Reaction of 4-({3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-pyridin-2-ylmethyl}-amino)-piperidine-1-carboxylic acid tert-butyl ester in CH2Cl2 with 3,5-dimethyl-pyridine-2-carbaldehyde and NaBH(OAc)3 gave 4-((3,5-dimethyl-pyridin-2-ylmethyl)-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-pyridin-2-ylmethyl}-amino)-piperidine-1-carboxylic acid tert-butyl ester as a white foam. 1H NMR (CDCl3) δ 1.25 (m, 3H), 1.43 (s, 9H), 1.61 (s+m, 8H), 2.24 (s, 3H), 2.28 (s, 3H), 2.39-2.47 (m, 3H), 3.35 (m, 1H), 3.66 (s, 2H), 4.02 (s, 2H), 6.87 (m, 4H), 7.19 (s, 2H), 7.82 (d, 1H, J=9.0 Hz), 8.10 (s, 1H), 8.51 (s, 1H). Deprotection with TFA using General Procedure F gave (3,5-dimethyl-pyridin-2-ylmethyl)-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-pyridin-2-ylmethyl}-piperidin-4-yl-amine as a pale yellow foam. 1H NMR (CDCl3) δ 1.56 (s+m, 9H), 1.76 (d, 2H, J=12.0 Hz), 2.21 (s, 3H), 2.28 (s, 3H), 2.52-2.67 (m, 3H), 3.18 (m, 1H), 3.41 (s, 2H), 3.57 (s, 2H), 6.83-6.90 (m, 4H), 7.20 (m, 2H), 7.82 (d, 1H, J=9.0 Hz), 8.09 (s, 1H), 8.49 (d, 1H, J=3.0 Hz). 13C NMR (CDCl3) δ 17.9, 18.4, 27.9, 31.1, 41.9, 42.2, 53.4, 54.1, 54.5, 57.0, 114.9, 115.2, 127.1, 127.2, 131.3, 132.7, 133.8, 138.7, 143.1, 145.5, 146.3, 146.6, 154.4, 158.1, 159.3, 162.5. HPLC: 90%. ES-MS m/z 447 [M+H]+. Anal. Calcd. for C28H35N4F.0.2 CH2Cl2: C, 73.06; H, 7.70; N, 12.09. Found: C, 73.19; H, 7.79; N, 12.10.

Quellen und Nachweise

ORD-Eintrag
ord-251f0df4378c41fd9ee4de8bf5aef48a
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07863293B2

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