1,2-Dichloroethane → (S)-tert-butyl 1-((4-(5-(2-methylbenzylcarbamoyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)thiophen-2-yl)methylamino)-1-oxopropan-2-ylcarbamate

HRID 2196503Notes

Reaction equation

HRID 2196503 reaction equation
[CH3:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][NH2:5].[C:10]([O:14][C:15]([NH:17][C@@H:18]([CH3:40])[C:19]([NH:21][CH2:22][C:23]1[S:27][CH:26]=[C:25]([N:28]2[C:32]([C:33](O)=[O:34])=[CH:31][C:30]([C:36]([F:39])([F:38])[F:37])=[N:29]2)[CH:24]=1)=[O:20])=[O:16])([CH3:13])([CH3:12])[CH3:11].C(Cl)CCl>ClCCl.CN(C1C=CN=CC=1)C>[CH3:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][NH:5][C:33]([C:32]1[N:28]([C:25]2[CH:24]=[C:23]([CH2:22][NH:21][C:19](=[O:20])[C@@H:18]([NH:17][C:15](=[O:16])[O:14][C:10]([CH3:13])([CH3:11])[CH3:12])[CH3:40])[S:27][CH:26]=2)[N:29]=[C:30]([C:36]([F:37])([F:39])[F:38])[CH:31]=1)=[O:34]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 69932-MethylbenzylamineHCID 69298555(S)-1-(5-((2-(tert-butoxycarbonylamino)propanamido)methyl)thiophen-3-yl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid

Product 1

HCID 69094615(S)-tert-butyl 1-((4-(5-(2-methylbenzylcarbamoyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)thiophen-2-yl)methylamino)-1-oxopropan-2-ylcarbamateYield 31%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-methylbenzylamine (0.037 mL, 0.295 mmol) and compound 7 (0.091 g, 0.197 mmol) in dichloromethane (2 mL) under nitrogen was added EDC (0.075 g, 0.394 mmol) followed by DMAP (9.62 mg, 0.079 mmol). The reaction was left to stir for 16 hours at room temperature. The solvent was then removed on the rotary evaporator and the brown material was purified by silica gel chromatography with a 12M Biotage column and a gradient of 0-5% methanol in dichloromethane to give 61.3 mg of a yellow crust. The sample was further purified by preparative HPLC (C18 Aquasil 20×250 mm; 40-85% methanol in water in 45 minutes at 10 mL/min) to afford compound 15a (34.4 mg, 31%) as a white crust. LRMS (ESI): calc. 565.2; found 466.1 (MH-Boc)+, 588.2 (MNa)+.

Workup

  1. waitThe reaction was left
  2. customThe solvent was then removed on the rotary evaporator
  3. customthe brown material was purified by silica gel chromatography with a 12M Biotage column
  4. customa gradient of 0-5% methanol in dichloromethane to give 61.3 mg of a yellow crust
  5. customThe sample was further purified by preparative HPLC (C18 Aquasil 20×250 mm; 40-85% methanol in water in 45 minutes at 10 mL/min)

Sources & evidence

ORD record
ord-40d2ccae7bf4431fa4ce9a4fccbbc8d8
Source dataset
uspto-grants-2012_12
Patent number
US08338437B2

Reaction notes

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