Diisopropylethylamine → HCID 67299851, compound

HRID 1806994Notes

Reaction equation

HRID 1806994 reaction equation
F[C:2](F)(F)[C:3]([OH:5])=[O:4].[Cl:8][C:9]1[C:10]([F:42])=[C:11]([CH:15]2[C:19]([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=3[F:29])([C:20]#[N:21])[CH:18]([CH2:30][C:31]3([CH2:37][OH:38])[CH2:36][CH2:35][CH:34]=[CH:33][CH2:32]3)[NH:17][CH:16]2[C:39]([OH:41])=O)[CH:12]=[CH:13][CH:14]=1.CN(C(O[N:51]1N=N[C:53]2[CH:54]=[CH:55]C=N[C:52]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:67]CN(C(C)C)C(C)C>C(Cl)Cl>[CH3:2][C:3]1([CH3:67])[O:5][C@@H:54]([CH2:53][CH2:52][NH:51][C:39]([CH:16]2[CH:15]([C:11]3[CH:12]=[CH:13][CH:14]=[C:9]([Cl:8])[C:10]=3[F:42])[C:19]([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=3[F:29])([C:20]#[N:21])[CH:18]([CH2:30][C:31]3([CH2:37][OH:38])[CH2:36][CH2:35][CH:34]=[CH:33][CH2:32]3)[NH:17]2)=[O:41])[CH2:55][O:4]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86640415HCID 86640415, compound

Product 1

HCID 67299851HCID 67299851, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(1-hydroxymethyl-cyclohex-3-enylmethyl)-pyrrolidine-2-carboxylic acid trifluoroacetic acid prepared in Example 117c (1 g, 1.6 mmol), HATU (1.07 g, 2.8 mmol) and iPr2NEt (1.37 mL, 7.8 mmol) in CH2Cl2 (10 mL) was stirred at room temperature for 18 h. The mixture was then diluted with CH2Cl2 and washed with water, brine. The organic layer was separated, the aqueous layer was extracted with CH2Cl2. The organic layers were combined, and concentrated. The residue was dissolved into tetrahydrofuran (5 mL), and aqueous saturated K2CO3 (5 mL) was added. The mixture was stirred at room temperature for 30 min, then partitioned between ethyl acetate and water. The organic layer was separated, washed with water, brine, dried over MgSO4 and concentrated. The residue was purified by flash chromatography (EtOAc) to give rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(1-hydroxymethyl-cyclohex-3-enylmethyl)-pyrrolidine-2-carboxylic acid [2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethyl]-amide as a white solid (0.48 g, 47%)

Workup

  1. washwashed with water, brine
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with CH2Cl2
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved into tetrahydrofuran (5 mL), and aqueous saturated K2CO3 (5 mL)
  6. additionwas added
  7. stirringThe mixture was stirred at room temperature for 30 min
  8. custompartitioned between ethyl acetate and water
  9. customThe organic layer was separated
  10. washwashed with water, brine
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated
  13. customThe residue was purified by flash chromatography (EtOAc)

Sources & evidence

ORD record
ord-76dc567734e14a95876355efba5d00e6
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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