Diisopropylethylamine → Methyl-3-(4-chlorophenyl)-2-{[4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzoyl]amino}propanoate

HRID 2090092Notes

Reaction equation

HRID 2090092 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:21]([CH3:23])[CH3:22])[C:6]2[O:10][C:9]([C:11]3[CH:19]=[CH:18][C:14]([C:15](O)=[O:16])=[CH:13][CH:12]=3)=[N:8][C:7]=2[CH:20]=1)#[N:2].[CH3:24][O:25][C:26]([CH:28]([NH2:37])[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=1)=[O:27].Cl.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.C(N(C(C)C)CC)(C)C>CN(C)C=O>[CH3:24][O:25][C:26](=[O:27])[CH:28]([NH:37][C:15](=[O:16])[C:14]1[CH:13]=[CH:12][C:11]([C:9]2[O:10][C:6]3[C:5]([CH:21]([CH3:23])[CH3:22])=[CH:4][C:3]([C:1]#[N:2])=[CH:20][C:7]=3[N:8]=2)=[CH:19][CH:18]=1)[CH2:29][C:30]1[CH:31]=[CH:32][C:33]([Cl:36])=[CH:34][CH:35]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 27332774-Chloro-DL-phenylalanine methyl ester hydrochlorideHCID 573699454-(5-Cyano-7-isopropylbenzo[d]oxazol-2-yl)benzoic acid2×

Product 1

HCID 25152583Methyl-3-(4-chlorophenyl)-2-{[4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzoyl]amino}propanoateYield 59.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

At room temperature, a 2-dram vial, equipped with a magnetic stirrer was charged with 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzoic acid (153 mg, 0.5 mmol, INTERMEDIATE 2), DL-4-chlorophenylalanine methyl ester hydrochloride (125 mg, 0.5 mmol), bromotrispyrrolidinophosphonium hexafluorophosphate (233 mg, 0.5 mmol) and 5 ml of dimethylformamide. To this was added diisopropylethylamine (524 μl, 3 mmol) dropwise, during which addition the reaction turned a reddish-orange. After a few minutes the reaction mixture faded to a pale yellow clear solution. The reaction mixture was allowed to stir at room temperature for 3 d. The residue was purified by chromatography using a Biotage SP1, 40M silica cartridge, eluting with a linear gradient of hexanes in ethyl acetate from 20% to 100% over 15 column volumes to provide the title compound as a white solid (150 mg). Mass spectrum (ESI) 502.2 (M+1). 1H NMR (600 MHz, CDCl3): δ 8.31 (d, J=8.2 Hz, 2H), 7.93 (d, J=1.2 Hz, 1H), 7.89 (d, J=8.4 Hz, 2H), 7.5 (s, 1H), 7.26 (d, J=8.2 Hz, 2H), 7.1 (d, J=8.3 Hz, 2H), 6.66 (d, J=7.3 Hz, 1H), 3.79 (s, 1H), 3.46 (m, 1H), 3.3 (dd, J=5.9, 5.9 Hz, 1H), 3.21 (dd, J=5.2, 5.0 Hz, 1H), 1.44 (J=6.9 Hz, 6H).

Workup

  1. customAt room temperature, a 2-dram vial, equipped with a magnetic stirrer
  2. additionduring which addition the reaction
  3. waitAfter a few minutes the reaction mixture faded to a pale yellow clear solution
  4. customThe residue was purified by chromatography
  5. washeluting with a linear gradient of hexanes in ethyl acetate from 20% to 100% over 15 column volumes

Sources & evidence

ORD record
ord-91ac5373618a4156a82a88ebfc51df97
Source dataset
uspto-grants-2013_05
Patent number
US08436028B2

Reaction notes

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