Diisopropylethylamine → HCID 86655579, compound

HRID 39280Notes

Reaction equation

HRID 39280 reaction equation
[C:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([P:12]([O:23][CH2:24][CH3:25])([CH2:14][P:15]([O:20][CH2:21][CH3:22])([O:17][CH2:18][CH3:19])=[O:16])=[O:13])=[CH:8][C:7]=1[C:26]([CH3:32])([CH3:31])[CH2:27][C:28](O)=[O:29])(=[O:4])[CH2:2][CH3:3].[CH3:33]CN(C(C)C)C(C)C.CN(C(ON1N=N[C:52]2[CH:53]=[CH:54][CH:55]=[CH:56][C:51]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.C([O:74][C:75](=[O:85])[C@H:76]([CH2:78][C:79]1[CH:84]=[CH:83][CH:82]=[CH:81][CH:80]=1)[NH2:77])C1C=CC=CC=1>CN(C=O)C.C(OCC)(=O)C>[CH2:33]([N:77]([C:28](=[O:29])[CH2:27][C:26]([C:7]1[CH:8]=[C:9]([P:12]([O:23][CH2:24][CH3:25])([CH2:14][P:15]([O:20][CH2:21][CH3:22])([O:17][CH2:18][CH3:19])=[O:16])=[O:13])[CH:10]=[CH:11][C:6]=1[O:5][C:1](=[O:4])[CH2:2][CH3:3])([CH3:31])[CH3:32])[C@H:76]([C:75]([OH:74])=[O:85])[CH2:78][C:79]1[CH:80]=[CH:81][CH:82]=[CH:83][CH:84]=1)[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12636208Benzyl L-phenylalaninate hydrochloride (1:1)HCID 86655578HCID 86655578, compound

Product 1

HCID 86655579HCID 86655579, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of acid 124 (319 mg, 0.648 mmol) in DMF (5 mL) at 0° C. was added DIEA (226 μL, 130 mmol) and HBTU (246 mg, 0.648 mmol). After stirring for 15 min at 0° C., L-Phenylalanine benzyl ester hydrochloride (189 mg, 0.648 mmol) was added and stirring was continued while warming to room temperature overnight. The reaction mixture was diluted with ethyl acetate, washed with H2O and saturated aqueous NaCl then dried over Na2SO4. The crude product was purified by silica gel chromatography (gradient of 0 to 20% methanol in ethyl acetate) using a Biotage Horizons™ system. Compound 125 was obtained as a colourless liquid (150 mg, 32%). 1H NMR (400 MHz, CDCl3) δ 1.20 (t, J=7.0, 3H), 1.21 (t, J=7.0, 3H), 1.25-1.32 (m, 18H), 1.44 (s, 3H), 1.45 (s, 3H), 1.47 (s, 3H), 1.48 (s, 3H), 2.47-2.67 (m, 12H), 2.87 (bd, J=6.2, 4H), 3.89-4.18 (m, 12H), 5.03 (AB q, J=12.3, 2H), 5.05 (AB q, J=12.3, 2H), 5.88 (bt, J=8.8, 2H), 6.91-6.95 (m, 4H), 7.01 (ddd, J=3.5, 5.2, 8.7, 2H), 7.17-7.23 (m, 10H), 7.31-7.32 (m, 6H), 7.71 (ddd, J=1.8, 8.1, 11.6, 1H), 7.75 (ddd, J=1.8, 8.1, 11.6, 1H), 7.86 (t, J=14.0, 1H), 7.87 (t, J=14.0, 1H): 31P (162 MHz, CDCl3) δ 20.31 (d, J=4.9, 1 P), 20.37 (d, J=4.9, 1 P), 33.93 (bd, J=9.5, 2P).

Workup

  1. stirringstirring
  2. temperaturewhile warming to room temperature overnight
  3. washwashed with H2O and saturated aqueous NaCl
  4. dry with materialthen dried over Na2SO4
  5. customThe crude product was purified by silica gel chromatography (gradient of 0 to 20% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-1803c4a5359a46dc9153a2507a5f8659
Source dataset
uspto-grants-2013_09
Patent number
US08524691B2

Reaction notes

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