Diisopropylethylamine → HCID 178427570, compound

HRID 591135Notes

Reaction equation

HRID 591135 reaction equation
[NH:1]([C:30]([O:32][CH2:33][CH:34]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:40]2[C:35]1=[CH:36][CH:37]=[CH:38][CH:39]=2)=[O:31])[C@H:2]([C:27](O)=[O:28])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:26])[NH:8][S:9]([C:12]1[C:24]([CH3:25])=[C:23]2[C:17]([O:18][C:19]([CH2:22]2)([CH3:21])[CH3:20])=[C:15]([CH3:16])[C:13]=1[CH3:14])(=[O:11])=[O:10].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:80]([O:84][C:85]([N:87]1[CH2:92][CH2:91][NH:90][CH2:89][CH2:88]1)=[O:86])([CH3:83])([CH3:82])[CH3:81]>CN(C=O)C>[C:80]([O:84][C:85]([N:87]1[CH2:92][CH2:91][N:90]([C:27](=[O:28])[C@@H:2]([NH:1][C:30]([O:32][CH2:33][CH:34]2[C:46]3[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=3[C:40]3[C:35]2=[CH:36][CH:37]=[CH:38][CH:39]=3)=[O:31])[CH2:3][CH2:4][CH2:5][NH:6]/[C:7](/[NH2:26])=[N:8]/[S:9]([C:12]2[C:13]([CH3:14])=[C:15]([CH3:16])[C:17]3[O:18][C:19]([CH3:21])([CH3:20])[CH2:22][C:23]=3[C:24]=2[CH3:25])(=[O:10])=[O:11])[CH2:89][CH2:88]1)=[O:86])([CH3:83])([CH3:81])[CH3:82]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178427572HCID 178427572, compound

Product 1

HCID 178427570HCID 178427570, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
5 °C

Procedure

To a solution of Fmoc-Arg(Pbf)-OH 1 (25.0 g, 38.5 mmol) in DMF (200 mL) at room temperature was added DIEA (13.41 mL, 77.1 mmol). After stiffing at room temperature for 10 min, the reaction mixture was cooled to ˜5° C. To the reaction mixture was added HATU (16.11 g, 42.4 mmol) in portions and stirred for 20 min and a solution of tert-butyl-1-piperazine carboxylate (7.18 g, 38.5 mmol) in DMF (50 mL) was added dropwise. The reaction mixture was stirred at ˜5° C. for 5 min. The mixture reaction was then allowed to warm to room temperature and stirred for 2 h. Solvent was removed in vacuo and the residue was dissolved in EtOAc (500 mL), washed with water (2×750 mL), 1% H2SO4 (300 mL) and brine (750 mL). The organic layer was separated, dried over Na2SO4 and solvent removed in vacuo to a total volume of 100 mL. Compound A was taken to the next step as EtOAc solution (100 mL). LC-MS [M+H] 817.5 (C43H56N6O8S+H, calc: 817.4).

Workup

  1. stirringThe reaction mixture was stirred at ˜5° C. for 5 min
  2. customThe mixture reaction
  3. temperatureto warm to room temperature
  4. stirringstirred for 2 h
  5. customSolvent was removed in vacuo
  6. dissolutionthe residue was dissolved in EtOAc (500 mL)
  7. washwashed with water (2×750 mL), 1% H2SO4 (300 mL) and brine (750 mL)
  8. customThe organic layer was separated
  9. dry with materialdried over Na2SO4 and solvent
  10. customremoved in vacuo to a total volume of 100 mL

Sources & evidence

ORD record
ord-0cdc748979fe4854b52e9861f05d8028
Source dataset
uspto-grants-2016_01
Patent number
US09238020B2

Reaction notes

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