Diisopropylethylamine → HCID 70149275, compound

HRID 2187890Notes

Reaction equation

HRID 2187890 reaction equation
Cl.[NH2:2][C@H:3]([CH3:19])[C:4]([N:6]([C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([OH:18])[CH:16]=2)[CH:11]=[CH:10][CH:9]=1)[CH3:7])=[O:5].[C:20]([C:22]1[CH:35]=[CH:34][C:25]([CH2:26][N:27]2[C:31]([CH:32]=O)=[CH:30][N:29]=[CH:28]2)=[CH:24][C:23]=1[F:36])#[N:21].C(N(CC)C(C)C)(C)C.[BH3-]C#N.[Na+]>CO.CC(O)=O>[C:20]([C:22]1[CH:35]=[CH:34][C:25]([CH2:26][N:27]2[C:31]([CH2:32][NH:2][C@H:3]([CH3:19])[C:4]([N:6]([C:8]3[C:17]4[C:12](=[CH:13][CH:14]=[C:15]([OH:18])[CH:16]=4)[CH:11]=[CH:10][CH:9]=3)[CH3:7])=[O:5])=[CH:30][N:29]=[CH:28]2)=[CH:24][C:23]=1[F:36])#[N:21]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 5003444Sodium cyanoborohydrideHCID 114247081-(4-Cyano-3-fluorobenzyl)-5-imidazolecarboxaldehydeHCID 69779597HCID 69779597, compound

Product 1

HCID 70149275HCID 70149275, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolvent2×HCID 887MethanolSolvent

Procedure

(R)-2-Amino-N-(7-hydroxynaphthalen-1yl)-N-methylpropionamide hydrochloride, as described above in Step D, (109 mg, 0.39 mmol) and 1-(4-cyano-3-fluorobenzyl)-5-imidazolecarboxaldehyde, as described in Example 4, Step G, (89 mg, 0.39 mmol), were stirred in MeOH (2 mL) and was neutralized with N,N-diisopropylethylamine. Acetic acid was then added dropwise to adjust the mixture to ca. pH 5, as judged by wetted pH paper. The mixture was stirred for 1 hr at ambient temperature, then NaCNBH3 (32 mg, 0.51 mmol) was added, the solution was readjusted to ca. pH 5 by addition of AcOH, and stirring was continued for 18 hrs. 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 CH2Cl2 (20 mL). The aqueous layer was extracted further with CH2Cl2 (2×20 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 1% to 6% MeOH −0.1% to 0.6% NH4OH —CH2Cl2 to yield the titled product.

Workup

  1. stirringstirring
  2. waitwas continued for 18 hrs
  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 CH2Cl2 (20 mL)
  6. extractionThe aqueous layer was extracted further with CH2Cl2 (2×20 mL)
  7. dry with materialThe combined organic extracts were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by flash column chromatography on silica
  11. washeluting with a gradient of 1% to 6% MeOH −0.1% to 0.6% NH4OH —CH2Cl2

Sources & evidence

ORD record
ord-1dcac3ce233f4d8cb9a58c60bd8e1a38
Source dataset
uspto-grants-2002_06
Patent number
US06410534B1

Reaction notes

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