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

HRID 251177Notes

Reaction equation

HRID 251177 reaction equation
[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].[Cl:32][C:33]1[CH:34]=[C:35]([CH3:41])[C:36]([CH:39]=O)=[N:37][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]([CH2:39][C:36]2[C:35]([CH3:41])=[CH:34][C:33]([Cl:32])=[CH:38][N:37]=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]

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 672721454-({3-[1-(4-Fluoro-phenyl)-1-methyl-ethyl]-pyridin-2-ylmethyl}-amino)-piperidine-1-carboxylic acid tert-butyl esterHCID 722140555-Chloro-3-methylpicolinaldehyde

Product 1

HCID 672723204-((5-Chloro-3-methyl-pyridin-2-ylmethyl)-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-pyridin-2-ylmethyl}-amino)-piperidine-1-carboxylic acid tert-butyl esterYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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 5-chloro-3-methyl-pyridine-2-carbaldehyde and NaBH(OAc)3 gave 4-((5-chloro-3-methyl-pyridin-2-ylmethyl)-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-pyridin-2-ylmethyl}-amino)-piperidine-1-carboxylic acid tert-butyl ester 0.558 g, 66%) as a white foam. 1H NMR (CDCl3) δ 1.21 (m, 2H), 1.44 (s, 9H), 1.60 (s+m, 9H), 2.24 (s, 3H), 2.39-2.51 (m, 3H), 3.33 (s, 2H), 3.66 (s, 2H), 4.02 (br s, 2H), 6.88 (m, 4H), 7.21 (dd, 1H, J=7.5, 3.0 Hz), 7.36 (s, 1H), 7.81 (d, 1H, J=9.0 Hz), 8.21 (d, 1H, J=3.0 Hz), 8.48 (d, 1H, J=3.0 Hz). Deprotection with TFA using General Procedure F gave (5-chloro-3-methyl-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 1.25-1.33 (m, 2H), 1.61 (s+m, 9H), 2.22 (s, 3H), 2.34-2.49 (m, 4H), 3.03 (d, 2H, J=12.0 Hz), 3.37 (s, 2H), 3.60 (s, 2H), 6.90 (m, 4H), 7.21 (dd, 1H, J=7.5, 3.0 Hz), 7.36 (s, 1H), 7.81 (d, 1H, J=9.0 Hz), 8.21 (d, 1H, J=3.0 Hz), 8.48 (d, 1H, J=3.0 Hz).

Sources & evidence

ORD record
ord-e427afadba714816b9583c01208d2022
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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