Diisopropylethylamine → HCID 10884289, compound

HRID 2306175Notes

Reaction equation

HRID 2306175 reaction equation
Cl.[NH2:2][C@@H:3]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([OH:15])[CH:10]=2)[C:4]1=[O:16].[C:17]([C:19]1[CH:32]=[CH:31][C:22]([CH2:23][N:24]2[C:28]([CH:29]=O)=[CH:27][N:26]=[CH:25]2)=[CH:21][C:20]=1[F:33])#[N:18].C(N(CC)C(C)C)(C)C.[BH3-]C#N.[Na+]>CO>[F:33][C:20]1[CH:21]=[C:22]([CH2:23][N:24]2[C:28]([CH2:29][NH:2][C@@H:3]3[CH2:7][CH2:6][N:5]([CH2:8][C:9]4[CH:14]=[CH:13][CH:12]=[C:11]([OH:15])[CH:10]=4)[C:4]3=[O:16])=[CH:27][N:26]=[CH:25]2)[CH:31]=[CH:32][C:19]=1[C:17]#[N:18]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 5003444Sodium cyanoborohydrideHCID 114247081-(4-Cyano-3-fluorobenzyl)-5-imidazolecarboxaldehydeHCID 70170716HCID 70170716, compound

Product 1

HCID 10884289HCID 10884289, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(R)-3-Amino-1-(3-hydroxybenzyl)-2-oxopyrrolidine hydrochloride, as described above in Step N, (200 mg, 0.82 mmol) and 1-(4-cyano-3-fluorobenzyl)-5-imidazolecarboxaldehyde, as described above in Step G, (197 mg, 0.86 mmol), were stirred in MeOH (7 mL) and N,N-diisopropylethylamine was added dropwise to 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 (54 mg, 0.86 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 (3 mL) and CH2Cl2 (10 mL). The aqueous layer was extracted further with CH2Cl2 (3×10 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 two column volumes of EtOAc—10% MeOH, then two column volumes of CHCl3—4% MeOH, then CHCl3—4% MeOH—0.4% NH4OH to yield the titled product as a colorless oil.

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 (3 mL) and CH2Cl2 (10 mL)
  6. extractionThe aqueous layer was extracted further with CH2Cl2 (3×10 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 two column volumes of EtOAc—10% MeOH

Sources & evidence

ORD record
ord-ede581c17bce4cb686f55e232f5e7744
Source dataset
uspto-grants-2002_08
Patent number
US06441017B1

Reaction notes

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