Triethylamine → rac-(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (3-carbamoyl-phenyl)-amide

HRID 417197Notes

Reaction equation

HRID 417197 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:40])[C@:10]3([C@@H:14]([C:15]4[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[C:16]=4[F:22])[C@H:13]([C:23]([NH:25][C:26]4[CH:27]=[C:28]([CH:32]=[CH:33][CH:34]=4)[C:29](O)=[O:30])=[O:24])[NH:12][C@H:11]3[CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[C:5]2=[CH:4][CH:3]=1.CC[N:43]=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.[NH4+].[Cl-]>>[C:29]([C:28]1[CH:27]=[C:26]([NH:25][C:23]([CH:13]2[NH:12][CH:11]([CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[C:10]3([C:5]4[C:6](=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)[NH:8][C:9]3=[O:40])[CH:14]2[C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[C:16]=2[F:22])=[O:24])[CH:34]=[CH:33][CH:32]=1)(=[O:30])[NH2:43]

Participants

6

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 53237509rac-3-{[(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carbonyl]amino}-benzoic acid

Product 1

HCID 75985871rac-(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (3-carbamoyl-phenyl)-amide

Procedure

In a manner similar to the method described in Example 22, rac-3-{[(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carbonyl]amino}-benzoic acid (42 mg, 0.072 mmol) was reacted with EDCI (28 mg, 0.14 mmol), HOBt (19 mg, 0.14 mmol), triethyamine (15 mg, 0.14 mmol), and NH4Cl (38 mg, 0.72 mmol) at 80° C. to give rac-(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid (3-carbamoyl-phenyl)-amide as a light yellow solid (Yield, 25 mg, 60%).

Workup

  1. customto give

Sources & evidence

ORD record
ord-6fa9eb868bee4c1495b99c9ddb95a9d1
Source dataset
uspto-grants-2012_01
Patent number
US08088815B2

Reaction notes

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