Diisopropylethylamine → di-tert-butyl (6-{[(4-phenyl-1-trityl-1H-imidazol-2-yl)(3-ethoxy-5-ethyl-2-fluorophenyl)methyl]amino}isoquinolin-1-yl)imidodicarbonate

HRID 2105090Notes

Reaction equation

HRID 2105090 reaction equation
Cl[CH:2]([C:33]1[CH:38]=[C:37]([CH2:39][CH3:40])[CH:36]=[C:35]([O:41][CH2:42][CH3:43])[C:34]=1[F:44])[C:3]1[N:4]([C:14]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:7]=1.CCN(C(C)C)C(C)C.[NH2:54][C:55]1[CH:56]=[C:57]2[C:62](=[CH:63][CH:64]=1)[C:61]([N:65]([C:73]([O:75][C:76]([CH3:79])([CH3:78])[CH3:77])=[O:74])[C:66]([O:68][C:69]([CH3:72])([CH3:71])[CH3:70])=[O:67])=[N:60][CH:59]=[CH:58]2>CC#N.C(Cl)Cl.CCOC(C)=O>[C:8]1([C:6]2[N:7]=[C:3]([CH:2]([NH:54][C:55]3[CH:56]=[C:57]4[C:62](=[CH:63][CH:64]=3)[C:61]([N:65]([C:66]([O:68][C:69]([CH3:72])([CH3:71])[CH3:70])=[O:67])[C:73]([O:75][C:76]([CH3:77])([CH3:78])[CH3:79])=[O:74])=[N:60][CH:59]=[CH:58]4)[C:33]3[CH:38]=[C:37]([CH2:39][CH3:40])[CH:36]=[C:35]([O:41][CH2:42][CH3:43])[C:34]=3[F:44])[N:4]([C:14]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH:5]=2)[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 58717298tert-butyl N-(6-aminoisoquinolin-1-yl)-N-[(tert-butoxy)carbonyl]carbamateHCID 68813235HCID 68813235, compound

Product 1

HCID 86607947di-tert-butyl (6-{[(4-phenyl-1-trityl-1H-imidazol-2-yl)(3-ethoxy-5-ethyl-2-fluorophenyl)methyl]amino}isoquinolin-1-yl)imidodicarbonateYield 84.8%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the chloro intermediate (1.80 mmol) in 5 mL CH3CN and 2 mL CH2Cl2 at rt, was added DIEA (0.627 mL, 3.6 mmol), di-tert-butyl (6-aminoisoquinolin-1-yl)imidodicarbonate (712 mg, 1.98 mmol). The mixture was stirred at rt for 19 h, then was diluted with EtOAc. The organic phase was washed with H2O (2×) and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 80% EtOAc/hexanes gradient) to afford 1.41 g of Intermediate 448.4 as an off-white solid. LCMS (2 min gradient) RT=2.32 min, 682.29 (M+(H−Tr)+H)+.

Workup

  1. washThe organic phase was washed with H2O (2×) and brine
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customThe crude product was purified by flash chromatography (0 to 80% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-b60f7cfd9af34ea2af0f8d5ca3742125
Source dataset
uspto-grants-2009_08
Patent number
US07576098B2

Reaction notes

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