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 1968706Notes

Reaction equation

HRID 1968706 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-7e7591aca08d4a0887be11d4f4c5f8fb
Source dataset
uspto-grants-2013_04
Patent number
US08426440B2

Reaction notes

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