Diisopropylethylamine → (S)-Benzyl 2-((S)-4-methyl-2-((S)-2-(2-morpholinoacetamido)-4-phenyl-N-((pivaloyloxy)methyl)butanamido) pentanamido)-3-phenylpropanoate

HRID 630634Notes

Reaction equation

HRID 630634 reaction equation
CCN(C(C)C)C(C)C.[CH3:10][CH:11]([CH3:47])[CH2:12][C@H:13]([N:17]([CH2:39][O:40][C:41](=[O:46])[C:42]([CH3:45])([CH3:44])[CH3:43])[C:18](=[O:38])[C@@H:19]([NH:28][C:29](=[O:37])[CH2:30][N:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1)[CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:14](O)=[O:15].[NH2:48][C@H:49]([C:57]([O:59][CH2:60][C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)=[O:58])[CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.O>[CH3:10][CH:11]([CH3:47])[CH2:12][C@H:13]([N:17]([CH2:39][O:40][C:41](=[O:46])[C:42]([CH3:45])([CH3:44])[CH3:43])[C:18](=[O:38])[C@@H:19]([NH:28][C:29](=[O:37])[CH2:30][N:31]1[CH2:32][CH2:33][O:34][CH2:35][CH2:36]1)[CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:14]([NH:48][C@@H:49]([CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)[C:57]([O:59][CH2:60][C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)=[O:58])=[O:15]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 736312Benzyl 3-phenyl-L-alaninateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86715393(S)-4-Methyl-2-((S)-2-(2-morpholinoacetamido)-4-phenyl-N-((pivaloyloxy)methyl)butanamido)pentanoic acid

Product 1

HCID 131735411(S)-Benzyl 2-((S)-4-methyl-2-((S)-2-(2-morpholinoacetamido)-4-phenyl-N-((pivaloyloxy)methyl)butanamido) pentanamido)-3-phenylpropanoateYield 67%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Referring to FIG. 45, DIPEA (270 μL, 1.6 mmol, 2.5 eq) was added to a mixture of acid (S)-4-methyl-2-((S)-2-(2-morpholinoacetamido)-4-phenyl-N-((pivaloyloxy)methyl)butanamido)pentanoic acid (345 mg, 0.64 mmol), H-Phe-OBn (283 mg, 0.97 mmol, 1.5 eq) and HATU (370 mg, 0.97 mmol, 1.5 eq) in CH2Cl2 (10 mL) and the mixture was stirred for four hours at RT. The mixture was poured into water and extracted twice with CH2Cl2. The combined organic extracts were dried over Na2SO4 and concentrated in vacuo. The residue was purified by chromatography (SiO2, 0-80% EtOAc in heptanes) and product (330 mg, 67%) was isolated as a colorless oil.

Workup

  1. extractionextracted twice with CH2Cl2
  2. dry with materialThe combined organic extracts were dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by chromatography (SiO2, 0-80% EtOAc in heptanes)

Sources & evidence

ORD record
ord-02dfce83917246b5bd6063e01df29712
Source dataset
uspto-grants-2016_04
Patent number
US09315542B2

Reaction notes

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