2-Dimethylaminopyridine → HCID 86704073, compound

HRID 2206382Notes

Reaction equation

HRID 2206382 reaction equation
[Cl:1][C:2]1[C:3]([F:45])=[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]([NH:30][C:31]2[CH:42]=[CH:41][C:34]([C:35]([O:37][CH2:38][CH2:39][OH:40])=[O:36])=[CH:33][C:32]=2[O:43][CH3:44])=[O:29])[CH:5]=[CH:6][CH:7]=1.[C:46]([O:50][C:51]([NH:53][CH:54]([CH3:58])[C:55](O)=[O:56])=[O:52])([CH3:49])([CH3:48])[CH3:47].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.CN(C1C=CC=CN=1)C>CN(C)C=O>[C:46]([O:50][C:51]([NH:53][C@H:54]([CH3:58])[C:55]([O:40][CH2:39][CH2:38][O:37][C:35](=[O:36])[C:34]1[CH:41]=[CH:42][C:31]([NH:30][C:28]([C@H:9]2[C@H:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=3[F:45])[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]([CH3:25])([CH3:26])[CH3:27])[NH:10]2)=[O:29])=[C:32]([O:43][CH3:44])[CH:33]=1)=[O:56])=[O:52])([CH3:49])([CH3:48])[CH3:47]

Participants

7

Reactant 5

HCID 218852-DimethylaminopyridineHCID 81531DiisopropylethylamineHCID 2684712-N-Boc-aminopropionic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 72550676HCID 72550676, compound

Product 1

HCID 86704073HCID 86704073, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a manner similar to the method described in Example 3, chiral 2-hydroxyethyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate (Example 1, 105.2 mg, 0.159 mmol) was reacted with (R)-(2-(tert-butoxycarbonylamino)propanoic acid (Chem-Impex, 75 mg, 0.398 mmol), HATU (Bachem, 151 mg, 0398 mmol), N,N-diisopropylethylamine (104 mg, 0.14 mL, 0.802 mmol) and dimethylaminopyridine (Aldrich, 10.8 mg, 0.088 mmol) in dimethyl formamide (8 mL) to give chiral 4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid 2-((R)-2-tert-butoxycarbonylamino-propionyloxy)-ethyl ester as a white solid (119 mg, 89% yield). MS (ES+) m/z calcd. for C41H47Cl2F2N4O8 [(M+H)+]: 831. found: 831.

Sources & evidence

ORD record
ord-e79d5080e3af4e1b8138a5f62e1758dc
Source dataset
uspto-grants-2016_06
Patent number
US09371280B2

Reaction notes

Loading…