Diethyl cyanophosphonate → (2-{4-[2-({5-[5-(2,6-dichloro-phenylmethanesulfonyl)-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carbonyl}-amino)-ethyl]-piperazin-1-yl}-1,1-dimethyl-2-oxo-ethyl)-carbamic acid tert-butyl ester

HRID 1359871Notes

Reaction equation

HRID 1359871 reaction equation
[N:1]1([CH2:7][CH2:8][NH:9][C:10]([C:12]2[C:16]([CH3:17])=[C:15](/[CH:18]=[C:19]3\[C:20](=[O:40])[NH:21][C:22]4[C:27]\3=[CH:26][C:25]([S:28]([CH2:31][C:32]3[C:37]([Cl:38])=[CH:36][CH:35]=[CH:34][C:33]=3[Cl:39])(=[O:30])=[O:29])=[CH:24][CH:23]=4)[NH:14][C:13]=2[CH3:41])=[O:11])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[C:42]([NH:49][C@@H:50]([C:52]([OH:54])=O)[CH3:51])([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43].[C:55](P(=O)(OCC)OCC)#N>C(Cl)Cl>[C:45]([O:44][C:42](=[O:43])[NH:49][C:50]([CH3:51])([CH3:55])[C:52]([N:4]1[CH2:5][CH2:6][N:1]([CH2:7][CH2:8][NH:9][C:10]([C:12]2[C:16]([CH3:17])=[C:15](/[CH:18]=[C:19]3\[C:20](=[O:40])[NH:21][C:22]4[C:27]\3=[CH:26][C:25]([S:28]([CH2:31][C:32]3[C:37]([Cl:38])=[CH:36][CH:35]=[CH:34][C:33]=3[Cl:39])(=[O:30])=[O:29])=[CH:24][CH:23]=4)[NH:14][C:13]=2[CH3:41])=[O:11])[CH2:2][CH2:3]1)=[O:54])([CH3:46])([CH3:47])[CH3:48]

Participants

5

Reactant 3

HCID 76257Diethyl cyanophosphonateHCID 637606BOC-D-alanineHCID 131723999HCID 131723999, compound

Product 1

HCID 69994415(2-{4-[2-({5-[5-(2,6-dichloro-phenylmethanesulfonyl)-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carbonyl}-amino)-ethyl]-piperazin-1-yl}-1,1-dimethyl-2-oxo-ethyl)-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Procedure

To a mixture of 5-[5-(2,6-dichloro-phenylmethanesulfonyl)-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-piperazin-1-yl-ethyl)-amide (150 mg, 0.24 mmol) and N-Boc D-alanine (19 mg, 1 eq.) in DCM (5 mL) cooled in an ice bath was added diethyl cyanophosphonate (48 mg, 1.2 eq.) in DCM (0.5 mL) followed by a dropwise addition of TEA (0.04 mL, 1 eq.) in DCM (0.5 mL). The mixture was then stirred at rt for overnight. The reaction was diluted with DCM, washed with 10% potassium carbonate, water, dried and concentrated to give (2-{4-[2-({5-[5-(2,6-dichloro-phenylmethanesulfonyl)-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carbonyl}-amino)-ethyl]-piperazin-1-yl}-1,1-dimethyl-2-oxo-ethyl)-carbamic acid tert-butyl ester as a red wax.

Workup

  1. temperaturecooled in an ice bath
  2. washwashed with 10% potassium carbonate, water
  3. customdried
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-41192d6bfabc4b039b7ed0bce1793680
Source dataset
uspto-grants-2003_07
Patent number
US06599902B2

Reaction notes

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