9-Fluorenylmethyl chloroformate → HCID 67344923, compound

HRID 1257736Notes

Reaction equation

HRID 1257736 reaction equation
[C:1](Cl)([O:3][CH2:4][CH:5]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]2[C:6]1=[CH:7][CH:8]=[CH:9][CH:10]=2)=[O:2].Cl.[C:20]1([S:26]([N:29]2[C:33]3=[N:34][CH:35]=[C:36]([N+:45]([O-:47])=[O:46])[C:37]([NH:38][CH:39]4[CH2:44][CH2:43][CH2:42][NH:41][CH2:40]4)=[C:32]3[CH:31]=[CH:30]2)(=[O:28])=[O:27])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[CH:16]1[C:17]2[CH:5]([CH2:4][O:3][C:1]([N:41]3[CH2:42][CH2:43][CH2:44][CH:39]([NH:38][C:37]4[C:36]([N+:45]([O-:47])=[O:46])=[CH:35][N:34]=[C:33]5[N:29]([S:26]([C:20]6[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=6)(=[O:28])=[O:27])[CH:30]=[CH:31][C:32]=45)[CH2:40]3)=[O:2])[C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[C:12]=2[CH:13]=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 343679-Fluorenylmethyl chloroformateHCID 81531DiisopropylethylamineHCID 67344293HCID 67344293, compound

Product 1

HCID 67344923HCID 67344923, compoundYield 93.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

Fmoc-Cl (3.16 g, 12.2 mmol) was added to a solution of crude (1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-yl)-piperidin-3-yl-amine hydrochloride (5.34 g, 12.2 mmol) and diisopropylethylamine (5.31 ml, 30.5 mmol) in CH2Cl2 (100 ml) at 0° C. The reaction mixture was warmed to 25° C. and stirred for 18 h, then was partitioned between half-saturated NaHCO3 (225 ml) and CH2Cl2 (2×200 ml). The combined organic layers were dried over MgSO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (gradient: 0 to 70% EtOAc in heptanes) to afford 3-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester (7.09 g, 93%) as a yellow solid. This material was used in the next step below without additional characterization or purification.

Workup

  1. customwas partitioned between half-saturated NaHCO3 (225 ml) and CH2Cl2 (2×200 ml)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by column chromatography on silica gel (gradient: 0 to 70% EtOAc in heptanes)

Sources & evidence

ORD record
ord-6540737a16b247da899a939ab83db57d
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

Loading…