Triethylamine → (S,R)-{2-oxo-1-phenyl-2-[3-(2-phenyl-imidazo[2,1-b]thiazol-6-ylcarbamoyl)-morpholin-4-yl]-ethyl}-carbamic acid tert-butyl ester

HRID 716515Notes

Reaction equation

HRID 716515 reaction equation
Cl.[C:2]1([C:8]2[S:12][C:11]3=[N:13][C:14]([NH:16][C:17]([C@@H:19]4[CH2:24][O:23][CH2:22][CH2:21][NH:20]4)=[O:18])=[CH:15][N:10]3[CH:9]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:25][C:26]([O:29][C:30]([NH:32][C@@H:33]([C:40](O)=[O:41])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31])([CH3:28])[CH3:27].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>ClCCl>[C:26]([O:29][C:30](=[O:31])[NH:32][C@@H:33]([C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[C:40](=[O:41])[N:20]1[CH2:21][CH2:22][O:23][CH2:24][C@@H:19]1[C:17](=[O:18])[NH:16][C:14]1[N:13]=[C:11]2[N:10]([CH:15]=1)[CH:9]=[C:8]([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[S:12]2)([CH3:28])([CH3:25])[CH3:27]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 2755953(2R)-2-{[(tert-butoxy)carbonyl]amino}-2-phenylacetic acidHCID 131730186(S)-morpholine-3-carboxylic acid (2-phenyl-imidazo[2,1-b]thiazol-6-yl)-amide, hydrochloride

Product 1

HCID 131730187(S,R)-{2-oxo-1-phenyl-2-[3-(2-phenyl-imidazo[2,1-b]thiazol-6-ylcarbamoyl)-morpholin-4-yl]-ethyl}-carbamic acid tert-butyl esterYield 6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Compound 16 (0.063 mmol), Boc-D-α-phenylglycine (0.126 mmol), and BOP (0.126) were added to dichloromethane (1.9 mL). Triethylamine (3.15 mmol) was added dropwise and the reaction mixture was stirred at room temperature overnight. The mixture was diluted in dichloromethane, washed sequentially with saturated solution of NaHCO3, water, and brine. The organic layers were gathered, dried, filtered, and concentrated under reduced pressure. The residue was purified by semi-preparative HPLC to give compound A22 as a white solid in 6% yield. 1H NMR (CDCl3, 400 MHz) δ (ppm) 1.41 (s, 2H), 1.44 (s, 7H), 1.83-2.09 (m, 1H), 2.64-3.90 (m, 4H), 4.33-4.68 (m, 1H), 5.19-6.09 (m, 2H), 7.29-7.45 (m, 9H), 7.50-7.582 (m, 2H), 7.60-7.64 (m, 1H); MS (ESI, EI+) m/z=562.29 (MH+).

Workup

  1. washwashed sequentially with saturated solution of NaHCO3, water, and brine
  2. customdried
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by semi-preparative HPLC
  6. customto give compound A22 as a white solid in 6% yield

Sources & evidence

ORD record
ord-4151284b75b64ee3b0e216d764b16434
Source dataset
uspto-grants-2015_11
Patent number
US09187496B2

Reaction notes

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