Triethylamine → 3-[2-(4-{4-[2-(3-Chlorophenylamino)-oxazol-5-yl]-phenyl}-cyclohexyl)-acetylamino]-propionic acid ethyl ester

HRID 1404232Notes

Reaction equation

HRID 1404232 reaction equation
[CH2:1]([O:3][C:4](=[O:8])[CH2:5][CH2:6][NH2:7])[CH3:2].CCN(CC)CC.[Cl:16][C:17]1[CH:18]=[C:19]([NH:23][C:24]2[O:25][C:26]([C:29]3[CH:34]=[CH:33][C:32]([CH:35]4[CH2:40][CH2:39][CH:38]([CH2:41][C:42](O)=[O:43])[CH2:37][CH2:36]4)=[CH:31][CH:30]=3)=[CH:27][N:28]=2)[CH:20]=[CH:21][CH:22]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O.O>[CH2:1]([O:3][C:4](=[O:8])[CH2:5][CH2:6][NH:7][C:42](=[O:43])[CH2:41][CH:38]1[CH2:37][CH2:36][CH:35]([C:32]2[CH:31]=[CH:30][C:29]([C:26]3[O:25][C:24]([NH:23][C:19]4[CH:20]=[CH:21][CH:22]=[C:17]([Cl:16])[CH:18]=4)=[N:28][CH:27]=3)=[CH:34][CH:33]=2)[CH2:40][CH2:39]1)[CH3:2]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 81531DiisopropylethylamineHCID 419889Ethyl 3-aminopropanoateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57899099(4-{4-[2-(3-Chlorophenylamino)-oxazol-5-yl]-phenyl}-cyclohexyl)-acetic acid

Product 1

HCID 666158633-[2-(4-{4-[2-(3-Chlorophenylamino)-oxazol-5-yl]-phenyl}-cyclohexyl)-acetylamino]-propionic acid ethyl esterYield 113%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-aminopropionic acid ethyl ester (41 mg, 0.268 mmol) and Et3N (0.082 mL, 0.730 mmol) is added a solution of (4-{4-[2-(3-Chlorophenylamino)-oxazol-5-yl]-phenyl}-cyclohexyl)-acetic acid (100 mg, 0.243 mmol) in DMF (4 mL), HATU (102 mg, 0.268 mmol) and iPr2NEt (0.127 mL, 0.73 mmol). The reaction mixture is allowed to stir at ambient temperature for 18 h. Water is added and EtOAc is used to extract. The organic layer is washed with brine, dried with Na2SO4 and concentrated to give the title compound (140 mg) as a tan solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 1.02-1.13 (m, 2 H) 1.18 (t, J=7.07Hz, 3 H) 1.38-1.50 (m, 2 H) 1.71 (dd, J=7.71, 4.17 Hz, 1 H) 1.78 (t, J=12.63Hz, 4 H) 1.98 (d, J=6.57 Hz, 2 H) 2.44 (t, J=6.82 Hz, 2 H) 3.25-3.28 (m, 2 H) 4.06 (q, J=7.07 Hz; 2 H) 6.99 (ddd, J=7.89, 1.96, 1.01 Hz, 1 H) 7.27-7.35 (m, 1 H) 7.29 (d, J=8.59 Hz, 2 H) 7.40 (s, 1H) 7.50 (d, J=8.34 Hz, 1 H) 7.47-7.52 (m, 1 H) 7.85 (t, J=2.02 Hz, 1 H) 7.88 (t, J=5.81 Hz, 1 H) 10.52 (s, 1H); (M+H)+ 510.2.

Workup

  1. extractionto extract
  2. washThe organic layer is washed with brine
  3. dry with materialdried with Na2SO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-f70ef87e13cf49bb8bffbabbb9272029
Source dataset
uspto-grants-2014_12
Patent number
US08912208B2

Reaction notes

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