Diisopropylethylamine → HCID 70171745, compound

HRID 2306223Notes

Reaction equation

HRID 2306223 reaction equation
[C:1]([C:3]1[CH:19]=[CH:18][C:6]([CH2:7][N:8]2[C:12]([CH2:13][CH2:14][C:15]([O-:17])=O)=[CH:11][N:10]=[CH:9]2)=[CH:5][C:4]=1[F:20])#[N:2].[Li+].Cl.[NH2:23][C@H:24]1[CH2:28][CH2:27][N:26]([C:29]2[C:38]3[C:33](=[CH:34][CH:35]=[C:36]([OH:39])[CH:37]=3)[CH:32]=[CH:31][CH:30]=2)[C:25]1=[O:40].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[C:1]([C:3]1[CH:19]=[CH:18][C:6]([CH2:7][N:8]2[C:12]([CH2:13][CH2:14][C:15]([NH:23][C@H:24]3[CH2:28][CH2:27][N:26]([C:29]4[C:38]5[C:33](=[CH:34][CH:35]=[C:36]([OH:39])[CH:37]=5)[CH:32]=[CH:31][CH:30]=4)[C:25]3=[O:40])=[O:17])=[CH:11][N:10]=[CH:9]2)=[CH:5][C:4]=1[F:20])#[N:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 23711715HCID 23711715, compoundHCID 70171920HCID 70171920, compound

Product 1

HCID 70171745HCID 70171745, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of lithium 3-[1-(4-cyano-3-fluorobenzyl)-1H-imidazol-5-yl]propionate, as described above in Step E (55 mg, 0.20 mmol), (S)-3-amino-1-(7-hydroxynaphthalen-1-yl)-2-oxopyrrolidine hydrochloride, as described in Example 9A, (56 mg, 0.20 mmol), PYBOP (105 mg, 0.20 mmol), and N,N-diisopropylethylamine (0.075 mL, 0.43 mmol) was stirred in DMF (0.5 mL) at ambient temperature for 4 hours. The reaction mixture was partitioned between saturated aqueous NaHCO3 (5 mL) and CHCl3 (10 mL). The aqueous layer was extracted further with CHCl3 (2×10 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography on silica, eluting with a gradient of CH2Cl2—1% MeOH—0.1% NH4OH to CH2Cl2—8% MeOH—0.8% NH4OH to yield the titled product.

Workup

  1. customThe reaction mixture was partitioned between saturated aqueous NaHCO3 (5 mL) and CHCl3 (10 mL)
  2. extractionThe aqueous layer was extracted further with CHCl3 (2×10 mL)
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash column chromatography on silica
  7. washeluting with a gradient of CH2Cl2—1% MeOH—0.1% NH4OH to CH2Cl2—8% MeOH—0.8% NH4OH

Sources & evidence

ORD record
ord-245b6880957c492981476d7997dc36ee
Source dataset
uspto-grants-2002_08
Patent number
US06441017B1

Reaction notes

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