4-(N-Boc-amino)piperidine → (1-{3-[5-Carbamoyl-4-(3-chloro-phenyl)-thiazol-2-ylamino]-4-nitro-benzyl}-piperidin-4-yl)-carbamic acid tert-butyl ester

HRID 1667703Notes

Reaction equation

HRID 1667703 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]([NH:16][C:17]3[CH:22]=[C:21]([CH:23]=O)[CH:20]=[CH:19][C:18]=3[N+:25]([O-:27])=[O:26])[S:11][C:12]=2[C:13]([NH2:15])=[O:14])[CH:5]=[CH:6][CH:7]=1.[C:28]([O:32][C:33](=[O:41])[NH:34][CH:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1)([CH3:31])([CH3:30])[CH3:29].C([BH3-])#N.[Na+]>ClCCl>[C:28]([O:32][C:33](=[O:41])[NH:34][CH:35]1[CH2:40][CH2:39][N:38]([CH2:23][C:21]2[CH:20]=[CH:19][C:18]([N+:25]([O-:27])=[O:26])=[C:17]([NH:16][C:10]3[S:11][C:12]([C:13](=[O:14])[NH2:15])=[C:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=4)[N:9]=3)[CH:22]=2)[CH2:37][CH2:36]1)([CH3:31])([CH3:29])[CH3:30]

Participants

5

Reactant 3

HCID 7238334-(N-Boc-amino)piperidineHCID 5003444Sodium cyanoborohydrideHCID 866428094-(3-Chloro-phenyl)-2-(5-formyl-2-nitro-phenylamino)-thiazole-5-carboxylic acid amide

Product 1

HCID 86642815(1-{3-[5-Carbamoyl-4-(3-chloro-phenyl)-thiazol-2-ylamino]-4-nitro-benzyl}-piperidin-4-yl)-carbamic acid tert-butyl esterYield 79.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 0.6 g (1.5 mmole) of 4-(3-chloro-phenyl)-2-(5-formyl-2-nitro-phenylamino)-thiazole-5-carboxylic acid amide (VI.2b) and 0.328 g (1.6 mmole) of piperidin-4-yl-carbamic acid tert-butyl ester in 15 mL of dichloromethane was added 0.477 g (2.3 mmole) of sodium cyanoborohydride. The mixture was stirred for 3 hours, then quenched by the addition of 25 ml, of water. The mixture was extracted three times with 50 mL of ethyl acetate. The combined ethyl acetate layers were washed once with 50 mL of brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with dichloromethane-methanol (gradient 100:0-80:20) to give 0.7 g of (1-{3-[5-carbamoyl-4-(3-chloro-phenyl)-thiazol-2-ylamino]-4-nitro-benzyl}-piperidin-4-yl)-carbamic acid tert-butyl ester (VI.12a).

Workup

  1. customquenched by the addition of 25 ml, of water
  2. extractionThe mixture was extracted three times with 50 mL of ethyl acetate
  3. washThe combined ethyl acetate layers were washed once with 50 mL of brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with dichloromethane-methanol (gradient 100:0-80:20)

Sources & evidence

ORD record
ord-6e54f8ea9ebf48f5bc3946eed7c7717e
Source dataset
uspto-grants-2011_10
Patent number
US08044213B2

Reaction notes

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