Diisopropylethylamine → HCID 91104069, compound

HRID 2187896Notes

Reaction equation

HRID 2187896 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[N:8]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]#[N:17])=[C:12]([F:18])[CH:11]=2)[CH:7]=[N:6][CH:5]=1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[Li+].[CH:53]([Si:56]([CH:78]([CH3:80])[CH3:79])([CH:75]([CH3:77])[CH3:76])[O:57][C:58]1[CH:67]=[C:66]2[C:61]([CH:62]=[CH:63][CH:64]=[C:65]2[C:68]([NH:70][CH2:71][C:72]([O-])=[O:73])=[O:69])=[CH:60][CH:59]=1)([CH3:55])[CH3:54].C(N(CC)C(C)C)(C)C>C1COCC1>[C:16]([C:13]1[CH:14]=[CH:15][C:10]([CH2:9][N:8]2[C:4]([CH2:3][NH:2][C:72]([CH2:71][NH:70][C:68]([C:65]3[C:66]4[C:61](=[CH:60][CH:59]=[C:58]([O:57][Si:56]([CH:75]([CH3:77])[CH3:76])([CH:53]([CH3:55])[CH3:54])[CH:78]([CH3:79])[CH3:80])[CH:67]=4)[CH:62]=[CH:63][CH:64]=3)=[O:69])=[O:73])=[CH:5][N:6]=[CH:7]2)=[CH:11][C:12]=1[F:18])#[N:17]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 18475874HCID 18475874, compoundHCID 69779784HCID 69779784, compound

Product 1

HCID 91104069HCID 91104069, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 5-(aminomethyl)-1-(4-cyano-3-fluorobenzyl)imidazole hydrochloride, as described above in Step B, (54 mg, 0.18 mmol) in dry THF (2 mL) under argon were added PYBOP (219 g, 0.42 mmol), N-[7-(triisopropylsilyloxy)naphthalene-1-carbonyl]glycine lithium salt, as described above in Step D, (171 mg, 0.42 mmol), and N,N-diisopropylethylamine (0.124 mL, 0.71 mmol). The reaction mixture was stirred for 3 hrs, then partitioned between CH2Cl2 (30 mL) and saturated aqueous NaHCO3 (10 mL). The aqueous layer was extracted further with CH2Cl2 (2×15 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica, eluting with a gradient of CH2Cl2-1% MeOH −0.1% NH4OH to CH2Cl2-5% MeOH −0.5% NH4OH, to yield the desired product as a pale foam.

Workup

  1. custompartitioned between CH2Cl2 (30 mL) and saturated aqueous NaHCO3 (10 mL)
  2. extractionThe aqueous layer was extracted further with CH2Cl2 (2×15 mL)
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography on silica
  7. washeluting with a gradient of CH2Cl2-1% MeOH −0.1% NH4OH to CH2Cl2-5% MeOH −0.5% NH4OH

Sources & evidence

ORD record
ord-c407e87dcc834131a7d85238ec6e7785
Source dataset
uspto-grants-2002_06
Patent number
US06410534B1

Reaction notes

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