Diphenylphosphinic chloride → Trifluoroacetic acid

HRID 417214Notes

Reaction equation

HRID 417214 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[Cl:8][C:9]1[CH:14]=[C:13]2[NH:15][C:16](=[O:38])[C:17]3([CH:21]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[C:23]=4[F:29])[CH:20]([C:30]([OH:32])=O)[NH:19][CH:18]3[CH2:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C:12]2=[CH:11][CH:10]=1.C(N(C(C)C)CC)(C)C.C1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1.[NH2:63][C:64]1[CH:68]=[CH:67][N:66]([CH2:69][C:70]([CH3:73])([OH:72])[CH3:71])[N:65]=1>>[OH:72][C:70]([CH3:73])([CH3:71])[CH2:69][N:66]1[CH:67]=[CH:68][C:64]([NH:63][C:30]([CH:20]2[NH:19][CH:18]([CH2:33][C:34]([CH3:36])([CH3:37])[CH3:35])[C:17]3([C:12]4[C:13](=[CH:14][C:9]([Cl:8])=[CH:10][CH:11]=4)[NH:15][C:16]3=[O:38])[CH:21]2[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[C:23]=2[F:29])=[O:32])=[N:65]1.[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4]

Participants

6

Reactant 4

HCID 73910Diphenylphosphinic chlorideHCID 81531DiisopropylethylamineHCID 593449381-(3-amino-1H-pyrazol-1-yl)-2-methylpropan-2-olHCID 78158843rac-(2'R,3'S,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 trifluoroacetic acid

Product 2

HCID 6422Trifluoroacetic acidHCID 75986084HCID 75986084, compound

Procedure

In a manner similar to the method described in Example 5, 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 trifluoroacetic acid prepared in Example 4 (0.25 g, 0.44 mmol), was reacted with diisopropylethylamine (0.23 g, 1.8 mmol), diphenylphosphinic chloride (0.32 g, 1.3 mmol), then reacted with 1-(3-amino-1H-pyrazol-1-yl)-2-methylpropan-2-ol (WO2009127544) (0.11 g, 0.67 mmol) at room temperature and purified by Prep-HPLC 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 [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide as a trifluoroacetic acid salt: white solid (Yield 62 mg, 20%).

Workup

  1. custompurified by Prep-HPLC

Sources & evidence

ORD record
ord-965822636e484e63a6544ac754f98113
Source dataset
uspto-grants-2012_01
Patent number
US08088815B2

Reaction notes

Loading…