Hydrochloric Acid → {(S)-4-({amino-[(E)-2,2,4,6,7-pentamethyl-2,3-dihydro-benzofuran-5-sulfonylimino]-methyl}-amino)-1-[2-(benzyloxycarbonyl-methyl-amino)-ethyl carbamoyl]-butyl}-carbamic acid tert-butyl ester

HRID 576552Notes

Reaction equation

HRID 576552 reaction equation
[NH:1]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[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].CN(C(ON1N=N[C:47]2[CH:48]=[CH:49][CH:50]=N[C:46]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:61]CN(C(C)C)C(C)C.[C:70]([O:74][C:75]([N:77]1[CH2:82]C[N:80](C(=O)[C@@H](NS(C2C=CC3C(=CC=CC=3)C=2)(=O)=O)CCCN/C(/N)=N/S(C2C(C)=C(C)C3OC(C)(C)CC=3C=2C)(=O)=O)[CH2:79][CH2:78]1)=[O:76])(C)(C)C.Cl>CN(C=O)C.CCOC(C)=O>[C:33]([O:32][C:30](=[O:31])[NH:1][C@H:2]([C:27](=[O:28])[NH:80][CH2:79][CH2:78][N:77]([C:75]([O:74][CH2:70][C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:61]=1)=[O:76])[CH3:82])[CH2:3][CH2:4][CH2:5][NH:6]/[C:7](/[NH2:26])=[N:8]/[S:9]([C:12]1[C:24]([CH3:25])=[C:23]([CH3:22])[C:17]2[O:18][C:19]([CH3:21])([CH3:20])[CH2:16][C:15]=2[C:13]=1[CH3:14])(=[O:10])=[O:11])([CH3:35])([CH3:34])[CH3:36]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178427604HCID 178427604, compoundHCID 178427607HCID 178427607, compound

Product 1

HCID 178427591{(S)-4-({amino-[(E)-2,2,4,6,7-pentamethyl-2,3-dihydro-benzofuran-5-sulfonylimino]-methyl}-amino)-1-[2-(benzyloxycarbonyl-methyl-amino)-ethyl carbamoyl]-butyl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of Boc-Arg(Pbf)-OH (3.33 g, 6.32 mmol), HATU (2.88 g, 7.58 mmol) and DIEA (7.4 mL, 31.6 mmol) in DMF (40 mL) was maintained at room temperature for 20 min, followed by the addition of compound C hydrochloride (1.45 g, 6.95 mmol). Stirring was continued for additional 1 h. The reaction mixture was diluted with EtOAc (500 mL) and extracted with water (3×75 mL) and brine (75 mL). The organic layer was dried over MgSO4 and then evaporated to provide compound AA (4.14 g, 5.77 mmol) as yellowish amorphous solid. LC-MS [M+H] 717.6 (C35H52N6O8S+H, calc: 717.9). Compound AA was used without further purification.

Workup

  1. extractionextracted with water (3×75 mL) and brine (75 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. customevaporated
  4. customto provide compound AA (4.14 g, 5.77 mmol) as yellowish amorphous solid
  5. customCompound AA was used without further purification

Sources & evidence

ORD record
ord-0e6e16d7ca434d4090f9ddcec7d625d0
Source dataset
uspto-grants-2015_05
Patent number
US09040032B2

Reaction notes

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