Triethylamine → N6-((4-(tert-butyldimethylsilyloxy)-5-ethyl-2-fluorophenyl)(2-methyl-5-phenyl-2H-1,2,4-triazol-3-yl)methyl)-N1,N1-di-(tert-butoxycarbonyl)isoquinoline-1,6-diamine

HRID 2105066Notes

Reaction equation

HRID 2105066 reaction equation
CS(OS(C)(=O)=O)(=O)=O.[Si:10]([O:17][C:18]1[C:23]([CH2:24][CH3:25])=[CH:22][C:21]([CH:26]([C:28]2[N:29]([CH3:39])[N:30]=[C:31]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[N:32]=2)O)=[C:20]([F:40])[CH:19]=1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11].CCN(CC)CC.[C:48]([O:52][C:53]([N:55]([C:67]([O:69][C:70]([CH3:73])([CH3:72])[CH3:71])=[O:68])[C:56]1[C:65]2[C:60](=[CH:61][C:62]([NH2:66])=[CH:63][CH:64]=2)[CH:59]=[CH:58][N:57]=1)=[O:54])([CH3:51])([CH3:50])[CH3:49]>C(Cl)Cl.O>[Si:10]([O:17][C:18]1[C:23]([CH2:24][CH3:25])=[CH:22][C:21]([CH:26]([C:28]2[N:29]([CH3:39])[N:30]=[C:31]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[N:32]=2)[NH:66][C:62]2[CH:61]=[C:60]3[C:65](=[CH:64][CH:63]=2)[C:56]([N:55]([C:53]([O:52][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:54])[C:67]([O:69][C:70]([CH3:71])([CH3:72])[CH3:73])=[O:68])=[N:57][CH:58]=[CH:59]3)=[C:20]([F:40])[CH:19]=1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 81560Methanesulfonic anhydrideHCID 57803708(4-(tert-butyldimethylsilyloxy)-5-ethyl-2-fluorophenyl)(2-methyl-5-phenyl-2H-1,2,4-triazol-3-yl)methanolHCID 58717298tert-butyl N-(6-aminoisoquinolin-1-yl)-N-[(tert-butoxy)carbonyl]carbamate

Product 1

HCID 57803686N6-((4-(tert-butyldimethylsilyloxy)-5-ethyl-2-fluorophenyl)(2-methyl-5-phenyl-2H-1,2,4-triazol-3-yl)methyl)-N1,N1-di-(tert-butoxycarbonyl)isoquinoline-1,6-diamineYield 54.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Methanesulfonic anhydride (184 mg, 1.3 mmol) was added to a solution of Intermediate 386.4 (292 mg, 0.66 mmol) and Et3N (0.30 mL, 2.2 mmol) in CH2Cl2 (5 mL) at 0° C. The mixture was stirred 1 h at 0° C., 1-(di-(tert-butyloxycarbonyl)amino)-6-aminoisoquinoline (475 mg, 1.3 mmol) was added and it was stirred 16 h at ambient temperature. Water (10 mL) was added and the mixture was extracted with EtOAc (3×25 mL). The organics were combined, washed with brine, dried (Na2SO4) and concentrated. Purification by flash chromatography (hexanes, EtOAc) yielded 280 mg of Intermediate 386.5 as a yellow solid. LCMS 783.53 (M+H).

Workup

  1. stirringit was stirred 16 h at ambient temperature
  2. extractionthe mixture was extracted with EtOAc (3×25 mL)
  3. washwashed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customPurification by flash chromatography (hexanes, EtOAc)

Sources & evidence

ORD record
ord-abc3e8d3f2bd4001b070fa23cb0fd24b
Source dataset
uspto-grants-2009_08
Patent number
US07576098B2

Reaction notes

Loading…