1-((Pyrrolidine-1-carbonyl)methyl)piperazine → HCID 86624984, compound

HRID 599510Notes

Reaction equation

HRID 599510 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16](=[O:33])[C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:28]([C:29]#[N:30])=[CH:27][C:26]([CH:31]=O)=[CH:25][N:24]=2)=[CH:19][CH:18]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:34]1([C:39]([CH2:41][N:42]2[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]2)=[O:40])[CH2:38][CH2:37][CH2:36][CH2:35]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[C:29]([C:28]1[C:23]([C:20]2[CH:19]=[CH:18][C:17]([C:16]([NH:15][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:33])=[CH:22][CH:21]=2)=[N:24][CH:25]=[C:26]([CH2:31][N:45]2[CH2:44][CH2:43][N:42]([CH2:41][C:39](=[O:40])[N:34]3[CH2:35][CH2:36][CH2:37][CH2:38]3)[CH2:47][CH2:46]2)[CH:27]=1)#[N:30]

Participants

5

Reactant 3

HCID 1006141-((Pyrrolidine-1-carbonyl)methyl)piperazineHCID 5049666Sodium triacetoxyborohydrideHCID 86624985HCID 86624985, compound

Product 1

HCID 86624984HCID 86624984, compoundYield 70.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-(2-t-Butoxycarbonylaminophenyl)-4-(3-cyano-5-formylpyridin-2-yl)benzamide (0.3 g, prepared as described in Method 15 below) and 1-(pyrrolidinocarbonylmethyl)piperazine (0.14 g) were dissolved in dichloromethane (10 ml). Sodium triacetoxyborohydride (0.15 g) was added, and the mixture stirred for 3 hours before being washed with water (10 ml). The organic residues were separated and purified using flash column chromatography eluting with ethyl acetate, followed by (6-8%) MeOH in dichloromethane to give t-butyl (2-{[4-(3-cyano-5-{[4-(2-oxo-2-pyrrolidin-1-ylethyl)piperazin-1-yl]methyl}pyridin-2-yl)benzoyl]amino}phenyl)carbamate (300 mg) as a pale yellow oil. The oil was dissolved in methanol (10 ml), and a 4M solution of hydrogen chloride in 1,4-dioxan (10 ml) added and the solution stirred at ambient temperature for 2 hours. The solvent was evaporated, methanol (5 ml) added and the resulting solution absorbed onto an SCX-2 column, which was then washed with methanol (2 column volumes) and the product eluted with a 2M solution of ammonia in methanol (2 column volumes). The ammonia/methanol was evaporated to give a foam. This was treated with diethyl ether (20 ml), stirred and filtered to give the product as a white solid (195 mg, 57%); NMR Spectrum: (DMSO-d6 373K) 1.82 (m, 4H), 2.50 (m, 8H), 3.11 (s, 2H), 3.40 (m, 4H), 3.66 (s, 2H), 4.74 (br s, 2H), 6.64 (m, 1H), 6.82 (m, 1H), 6.98 (m, 1H), 7.27 (m, 1H), 7.99 (d, 2H), 8.13 (d, 2H), 8.24 (d, 1H), 8.87 (d, 1H), 9.49 (br s, 1H); Mass Spectrum: M+H+ 524.

Workup

  1. washbefore being washed with water (10 ml)
  2. customThe organic residues were separated
  3. custompurified
  4. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-b42e4321aa1a43a998bbe6f2a7b52f93
Source dataset
uspto-grants-2011_03
Patent number
US07897778B2

Reaction notes

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