Triethylamine → {(R)-3-[(R)-2-((S)-2-Amino-3-phenyl-propionylamino)-3-methyl-butyrylamino]-2-hydroxy-propyl}-cyclohexylmethyl-phosphinic acid

HRID 1926992Notes

Reaction equation

HRID 1926992 reaction equation
C([O:8][P:9]([CH2:18][C@H:19]([OH:50])[CH2:20][NH:21][C:22](=[O:49])[C@@H:23]([NH:27][C:28](=[O:48])[C@@H:29]([NH:37]C(OCC1C=CC=CC=1)=O)[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH:24]([CH3:26])[CH3:25])([CH2:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)=[O:10])C1C=CC=CC=1.C(OP(C[C@H](O)CNC(=O)[C@H](NC(=O)[C@@H](NC(OCC1C=CC=CC=1)=O)CC1C=CC=CC=1)C(C)C)(CC1CCCCC1)=O)C1C=CC=CC=1.N(C(OCC1C=CC=CC=1)=O)[C@H](C(N[C@H](C(O)=O)C(C)C)=O)CC1C=CC=CC=1.OC1C2N=NNC=2C=CC=1.N=C=N.C(N(CC)CC)C.Cl.C(OP(C[C@H](O)CN)(CC1CCCCC1)=O)C1C=CC=CC=1>C(Cl)Cl>[NH2:37][C@@H:29]([CH2:30][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)[C:28]([NH:27][C@H:23]([CH:24]([CH3:25])[CH3:26])[C:22]([NH:21][CH2:20][C@@H:19]([OH:50])[CH2:18][P:9]([CH2:11][CH:12]1[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]1)(=[O:8])[OH:10])=[O:49])=[O:48]

Participants

9

Reactant 7

HCID 8471TriethylamineHCID 160435CarbodiimideHCID 6992356N-((Phenylmethoxy)carbonyl)-L-phenylalanyl-L-valineHCID 68622017{(R)-3-[(S)-2-((S)-2-Benzyloxycarbonylamino-3-phenyl-propionylamino)-3-methyl-butyrylamino]-2-hydroxy-propyl}-cyclohexylmethyl-phosphinic acid benzyl esterHCID 68622110((R)-3-amino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid benzyl ester hydrochlorideHCID 68622613{(R)-3-[(R)-2-((S)-2-benzyloxycarbonylamino-3-phenyl-propionylamino)-3-methyl-butyrylamino]-2-hydroxy-propyl}-cyclohexylmethyl-phosphinic acid benzyl esterHCID 178418300HCID 178418300, compound

Product 1

HCID 11684426{(R)-3-[(R)-2-((S)-2-Amino-3-phenyl-propionylamino)-3-methyl-butyrylamino]-2-hydroxy-propyl}-cyclohexylmethyl-phosphinic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

{(R)-3-[(S)-2-((S)-2-Benzyloxycarbonylamino-3-phenyl-propionylamino)-3-methyl-butyrylamino]-2-hydroxy-propyl}-cyclohexylmethyl-phosphinic acid benzyl ester and {(R)-3-[(R)-2-((S)-2-benzyloxycarbonylamino-3-phenyl-propionylamino)-3-methyl-butyrylamino]-2-hydroxy-propyl}-cyclohexylmethyl-phosphinic acid benzyl ester: To a solution of N-Z-Phe-Val-OH (1.0 g, 2.5 mmol) dissolved in CH2Cl2 (80 mL) under nitrogen was added hydroxybenzotriazole (0.346 g, 2.56 mmol) and PS-Carbodiimide (1.3 g, 3.0 mmol). After stirring for 10 min, triethylamine (1.4 mL, 10 mmol) and ((R)-3-amino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid benzyl ester hydrochloride (1.36 g, 3.75 mmol) were added. The reaction was stirred for 2 h, then filtered and concentrated in vacuo. The residue was purified by flash chromatography using 0-4% MeOH/CH2Cl2 as the eluent on a 35 g RediSep disposable column to give the title compound (0.806 g, 1.14 mmol) as a glassy solid. 31P NMR (CD3OD, 300 MHz): δ 59.09, 59.09, 58.38, 58.38. LCMS m/z: [M+H]+=707.

Workup

  1. stirringThe reaction was stirred for 2 h
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-95edd91cd084459394a052f1a0b54031
Source dataset
uspto-grants-2012_05
Patent number
US08183231B2

Reaction notes

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