Ethanamine, 2,2'-[oxybis(2,1-ethanediyloxy)]bis- → HCID 72548872, compound

HRID 2206439Notes

Reaction equation

HRID 2206439 reaction equation
[Cl:1][C:2]1[C:3]([F:42])=[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:39]=[CH:38][C:34]([C:35]([OH:37])=O)=[CH:33][C:32]=2[O:40][CH3:41])=[O:29])[CH:5]=[CH:6][CH:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:67][CH2:68][CH2:69][O:70][CH2:71][CH2:72][O:73][CH2:74][CH2:75][O:76][CH2:77][CH2:78][NH2:79]>O1CCCC1>[NH2:79][CH2:78][CH2:77][O:76][CH2:75][CH2:74][O:73][CH2:72][CH2:71][O:70][CH2:69][CH2:68][NH:67][C:35]([C:34]1[CH:38]=[CH:39][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:42])[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]2)=[O:29])=[C:32]([O:40][CH3:41])[CH:33]=1)=[O:37]

Participants

5

Reactant 3

HCID 70250Ethanamine, 2,2'-[oxybis(2,1-ethanediyloxy)]bis-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 53358942Idasanutlin

Product 1

HCID 72548872HCID 72548872, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

In a 20 mL round-bottomed flask, 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoic acid (prepared as described in US20100152190A1, 200 mg, 324 μmol) and HATU (136 mg, 357 μmol) combined with dry tetrahydrofuran (2 mL) to give an off-white suspension at room temperature. It was stirred for 30 min at room temperature. The reaction mixture was slowly added dropwise to a solution of 1,11-diamino-3,6,9-trioxaundecane (312 mg, 304 μL, 1.62 mmol) in dry tetrahydrofuran (1.5 mL) at 0° C. The reaction was done after stirring at room temperature for 20 min. It was filtered and injected into Gilson reverse-phase high-performance liquid chromatography for purification. The desired fractions was converted to free base and lyophilized to afford (2R,3S,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid [4-(2-{2-[2-(2-amino-ethoxy)-ethoxy]-ethoxy}-ethylcarbamoyl)-2-methoxy-phenyl]-amide as a white solid (169 mg, 66% yield). LCMS (ES+) m/z calcd. for C39H47Cl2F2N5O6 [(M+H)+]: 790. found: 790.

Workup

  1. customto give an off-white suspension at room temperature
  2. stirringafter stirring at room temperature for 20 min
  3. filtrationIt was filtered
  4. custominjected into Gilson reverse-phase high-performance liquid chromatography for purification

Sources & evidence

ORD record
ord-4d06a06b4859476a99c4b87617f8714c
Source dataset
uspto-grants-2016_06
Patent number
US09371280B2

Reaction notes

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