Ammonium Chloride → (7-Chloro-8-[4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-naphthalen-2-ylmethyl)-(2-fluoro-ethyl)-carbamic acid tert-butyl ester

HRID 505192Notes

Reaction equation

HRID 505192 reaction equation
[C:1]([O:5][C:6](=[O:27])[N:7]([CH2:11][C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[C:15]([CH2:23][C:24](=[O:26])[NH2:25])[C:16]([Cl:22])=[CH:17][CH:18]=2)[CH:13]=1)[CH2:8][CH2:9][F:10])([CH3:4])([CH3:3])[CH3:2].C[O:29][C:30](=O)[C:31]([C:33]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[N:35]([CH3:42])[CH:34]=1)=O.CC([O-])(C)C.[K+].[NH4+].[Cl-]>C1COCC1.CCOC(C)=O.O>[C:1]([O:5][C:6](=[O:27])[N:7]([CH2:11][C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[C:15]([C:23]3[C:24](=[O:26])[NH:25][C:30](=[O:29])[C:31]=3[C:33]3[C:41]4[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=4)[N:35]([CH3:42])[CH:34]=3)[C:16]([Cl:22])=[CH:17][CH:18]=2)[CH:13]=1)[CH2:8][CH2:9][F:10])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 44536752-(1-Methyl-1H-indol-3-YL)-2-oxoacetic acid methyl esterHCID 23665647Potassium tert-butoxideHCID 86625784(8-Carbamoylmethyl-7-chloro-naphthalen-2-ylmethyl)-(2-fluoro-ethyl)-carbamic acid tert-butyl ester

Product 1

HCID 86625783(7-Chloro-8-[4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-naphthalen-2-ylmethyl)-(2-fluoro-ethyl)-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

(8-Carbamoylmethyl-7-chloro-naphthalen-2-ylmethyl)-(2-fluoro-ethyl)-carbamic acid tert-butyl ester (80 mg, 0.20 mmol) and (1-methyl-1H-indol-3-yl)-oxo-acetic acid methyl ester (57 mg, 0.26 mmol) are dissolved under an atmosphere of argon in dry THF (4 ml). Activated molecular sieves 3 Å (100 mg) is added. After 10 minutes at RT, a solution of 1.0 M KOtBu in THF (0.61 ml, 0.61 mmol) is added in one portion. The reaction mixture is diluted with EtOAc and poured into a saturated aqueous NH4Cl solution. The organic layer is separated, washed with brine, dried over Na2SO4 and concentrated. The residue is directly used in the next reaction. ES+-MS: 579.2, 580.5 [M+H+H2O]+. ES−-MS: 560.2, 561.5 [M−H]−.

Workup

  1. additionActivated molecular sieves 3 Å (100 mg) is added
  2. customThe organic layer is separated
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue is directly used in the next reaction

Sources & evidence

ORD record
ord-34e28f76621e40d1b7c433c30624b9ff
Source dataset
uspto-grants-2010_08
Patent number
US07781438B2

Reaction notes

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