2,6-Lutidine → 1,1-Dioxo-3-butyl-3-ethyl-5-phenyl-7-bromo-8-(2-{N-[(R)-alpha-(t-butoxycarbonyl)benzyl]carbamoyl}ethoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine

HRID 458930Notes

Reaction equation

HRID 458930 reaction equation
[O:1]=[S:2]1(=[O:32])[C:8]2[CH:9]=[C:10]([O:14][CH2:15][CH2:16][C:17](O)=[O:18])[C:11]([Br:13])=[CH:12][C:7]=2[N:6]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:5][C:4]([CH2:28][CH2:29][CH2:30][CH3:31])([CH2:26][CH3:27])[CH2:3]1.[C:33]([O:37][C:38]([C@H:40]([NH2:47])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:39])([CH3:36])([CH3:35])[CH3:34].N1C(C)=CC=CC=1C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(Cl)Cl>[O:32]=[S:2]1(=[O:1])[C:8]2[CH:9]=[C:10]([O:14][CH2:15][CH2:16][C:17](=[O:18])[NH:47][C@@H:40]([C:38]([O:37][C:33]([CH3:36])([CH3:34])[CH3:35])=[O:39])[C:41]3[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=3)[C:11]([Br:13])=[CH:12][C:7]=2[N:6]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:5][C:4]([CH2:28][CH2:29][CH2:30][CH3:31])([CH2:26][CH3:27])[CH2:3]1

Participants

6

Reactant 4

HCID 79372,6-LutidineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 7015059tert-butyl (2R)-2-amino-2-phenylacetateHCID 223931131,1-Dioxo-3-butyl-3-ethyl-5-phenyl-7-bromo-8-(2-carboxyethoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine

Product 1

HCID 693605551,1-Dioxo-3-butyl-3-ethyl-5-phenyl-7-bromo-8-(2-{N-[(R)-alpha-(t-butoxycarbonyl)benzyl]carbamoyl}ethoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepineYield 89%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1,1-dioxo-3-butyl-3-ethyl-5-phenyl-7-bromo-8-(2-carboxyethoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine (Method 89; 70 mg, 0.134 mmol) and (R)-α-(t-butoxycarbonyl)benzylamine (J. Amer. Chem. Soc.; EN; 117; 44; 1995; 10879–10888; 35 mg, 0.169 mmol) in DCM (2.5 ml) was added 2,6-lutidine (29 mg, 0.268 mmol) and TBTU (56 mg, 0.174 mmol). The reaction mixture was stirred at room temperature for 2.5 hours, then diluted with DCM. The solution was washed with NaHCO3 (aq, sat), water, dried and the solvent was evaporated under reduced pressure. The residue was suspended in ether/petroleum ether and the crystals filtered to give the title compound 85 mg (89%). NMR (500 MHz) 0.79–0.86 (m, 6H), 1.04–1.28 (m, 4H), 1.35–1.56 (m, 11H), 1.60–1.77 (m, 2H), 2.82 (t, 2H), 3.13–3.25 (m, 2H), 3.72 (brs, 2H), 4.35–4.44 (m, 2H), 5.54 (d, 1H), 6.95 (d, 1H), 7.04 (t, 1H), 7.08 (d, 2H), 7.15 (s, 1H), 7.29–7.43 (m, 6H), 7.52 (s, 1H).

Workup

  1. washThe solution was washed with NaHCO3 (aq, sat), water
  2. customdried
  3. customthe solvent was evaporated under reduced pressure
  4. filtrationthe crystals filtered

Sources & evidence

ORD record
ord-a970352214d8487c8fe1445ef7d7225e
Source dataset
uspto-grants-2007_03
Patent number
US07192945B2

Reaction notes

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