Diisopropylethylamine → HCID 53358231, compound

HRID 1807304Notes

Reaction equation

HRID 1807304 reaction equation
[Cl:1][C:2]1[C:3]([F:31])=[C:4]([C@@H:8]2[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][C@H:9]2[C:28]([OH:30])=O)[CH:5]=[CH:6][CH:7]=1.C(N(CC)C(C)C)(C)C.Cl.[NH2:42][C:43]1[CH:48]=[CH:47][C:46]([N:49]2[CH2:53][CH2:52][CH2:51][CH:50]2[C:54]([O:56][CH3:57])=[O:55])=[CH:45][CH:44]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl>[Cl:1][C:2]1[C:3]([F:31])=[C:4]([C@@H:8]2[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:26])([CH3:25])[CH3:27])[NH:10][C@H:9]2[C:28]([NH:42][C:43]2[CH:48]=[CH:47][C:46]([N:49]3[CH2:53][CH2:52][CH2:51][CH:50]3[C:54]([O:56][CH3:57])=[O:55])=[CH:45][CH:44]=2)=[O:30])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59249226(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxylic acidHCID 67367356HCID 67367356, compound

Product 1

HCID 53358231HCID 53358231, compoundYield 84.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxylic acid (60 mg, 0.128 mmole) in dichloromethane (6 ml) were added N,N-DIISOPROPYLETHYLAMINE (104 mg, 140 μl, 0.802 mmol) and methyl 1-(4-aminophenyl)pyrrolidine-2-carboxylate hydrochloride (50.2 mg, 0.196 mmol, Beta Pharma) followed by N,N,N′,N′-tetramethyl-O-(7-aza-benzotriazol-1-yl)uranium hexafluorophosphate (HATU) (90.3 mg, 0237 mmole, Chem-Impex) and the reaction mixture was stirred at rt for 1 hr. The reaction mixture was diluted with CH2Cl2 (80 mL), washed with sat Na2CO3 (2×15 mL), water (2×15 mL) and evaporated. The crude material was purified by flash chromatography (silica gel, 4 g, 5% to 100% EtOAc in hexanes) to give methyl 1-(4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)phenyl)pyrrolidine-2-carboxylate (72.4 mg, 84%) as a white solid. MS (ES+) m/z Calcd: [(M+H)+]: 669. found: 669.

Workup

  1. washwashed
  2. customevaporated
  3. customThe crude material was purified by flash chromatography (silica gel, 4 g, 5% to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-84f1dc60b752438bb9957aa688abf2ee
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

Loading…