Diisopropylethylamine → HCID 70170748, compound

HRID 2306183Notes

Reaction equation

HRID 2306183 reaction equation
Cl.[NH2:2][C@@H:3]1[CH2:7][CH2:6][N:5]([S:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([OH:17])[CH:12]=2)(=[O:10])=[O:9])[CH2:4]1.[C:18]([C:20]1[CH:33]=[CH:32][C:23]([CH2:24][N:25]2[C:29]([CH:30]=O)=[CH:28][N:27]=[CH:26]2)=[CH:22][C:21]=1[F:34])#[N:19].C(N(CC)C(C)C)(C)C.[BH3-]C#N.[Na+]>CO>[F:34][C:21]1[CH:22]=[C:23]([CH2:24][N:25]2[C:29]([CH2:30][NH:2][C@@H:3]3[CH2:7][CH2:6][N:5]([S:8]([C:11]4[CH:16]=[CH:15][CH:14]=[C:13]([OH:17])[CH:12]=4)(=[O:10])=[O:9])[CH2:4]3)=[CH:28][N:27]=[CH:26]2)[CH:32]=[CH:33][C:20]=1[C:18]#[N:19]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 5003444Sodium cyanoborohydrideHCID 114247081-(4-Cyano-3-fluorobenzyl)-5-imidazolecarboxaldehydeHCID 70166517HCID 70166517, compound

Product 1

HCID 70170748HCID 70170748, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(R)-3-Amino-1-(3-hydroxyphenylsulfonyl)pyrrolidine hydrochloride, as described above in Step F. (360 mg, 1.29 nimol) and 1-(4-cyano-3-fluorobenzyl)-5-imidazolecarboxaldehyde, as described in Example 1, Step G. (326 mg, 1.42 mmol) were stirred in MeOH (8 mL) and N,N-diisopropylethylamine was added dropwise adjust the mixture to ca. pH 5, as judged by wetted pH paper. The mixture was stirred for 1 hour at ambient temperature then NaCNBH3 (97 mg, 1.54 mmol) was added and stirring was continued for 18 hours. The reaction was quenched with saturated aqueous NaHCO3 (2 mL) and most of the MeOH was removed under reduced pressure. The residual solution was partitioned between saturated aqueous NaHCO3 (10 mL) and CHCl3 (20 mL). The aqueous layer was extracted further with CHCl3 (3×15 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography on silica, eluting with a gradient of EtOAc—5% MeOH—0.5% NH4OH to EtOAc—10% MeOH—1% NH4OH to yield the titled product as a white foam.

Workup

  1. stirringstirring
  2. waitwas continued for 18 hours
  3. customThe reaction was quenched with saturated aqueous NaHCO3 (2 mL) and most of the MeOH
  4. customwas removed under reduced pressure
  5. customThe residual solution was partitioned between saturated aqueous NaHCO3 (10 mL) and CHCl3 (20 mL)
  6. extractionThe aqueous layer was extracted further with CHCl3 (3×15 mL)
  7. dry with materialThe combined organic extracts were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by flash column chromatography on silica
  11. washeluting with a gradient of EtOAc—5% MeOH—0.5% NH4OH to EtOAc—10% MeOH—1% NH4OH

Sources & evidence

ORD record
ord-4a83a083290f485c812bd286f933778b
Source dataset
uspto-grants-2002_08
Patent number
US06441017B1

Reaction notes

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