1,2-Dichloroethane → HCID 59271827, compound

HRID 1893190Notes

Reaction equation

HRID 1893190 reaction equation
Cl.[F:2][C:3]1[CH:29]=[CH:28][C:6]([CH2:7][NH:8][C:9]([C:11]2[N:12]=[C:13]3C(NC)[CH2:18][CH2:17][C:16]([CH3:23])([CH3:22])[CH2:15][N:14]3[C:24](=[O:27])[C:25]=2[OH:26])=[O:10])=[CH:5][C:4]=1[CH3:30].C1[CH:36]=[N:35][C:34]2N(O)N=NC=2C=1.[CH3:41][N:42]([CH3:48])[C:43](=[O:47])[C:44]([OH:46])=O.C(N(CC)CC)C.C(Cl)CCl>ClCCl.CCOC(C)=O>[F:2][C:3]1[CH:29]=[CH:28][C:6]([CH2:7][NH:8][C:9]([C:11]2[N:12]=[C:13]3[CH:41]([N:42]([CH3:48])[C:43](=[O:47])[C:44]([N:35]([CH3:36])[CH3:34])=[O:46])[CH2:18][CH2:17][C:16]([CH3:23])([CH3:22])[CH2:15][N:14]3[C:24](=[O:27])[C:25]=2[OH:26])=[O:10])=[CH:5][C:4]=1[CH3:30]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 181649HOAtHCID 2760995N,N-Dimethyloxamic acidHCID 68617853HCID 68617853, compound

Product 1

HCID 59271827HCID 59271827, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of N-(4-fluoro-3-methylbenzyl)-3-hydroxy-7,7-dimethyl-10-(methylamino)-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepine-2-carboxamide hydrochloride (200 mg, 0.421 mmol), HOAt (68.7 mg, 0.5 mmol), N,N-dimethyloxamic acid (74 mg, 0.631 mmol) and triethylamine (0.235 mL, 1.683 mmol), in dichloromethane (5 mL) was added EDC (224 mg, 1.262 mmol). The mixture was stirred at room temperature under nitrogen overnight, diluted with 25 mL EtOAc, washed with 10 mL each of saturated NaHCO3 solution, H2O, and brine, and dried over Na2SO4. Concentration gave a crude title product which was purifried by preparative reverse phase chromatography (gradient elution 0.1% AcOH in water/acetonitrile) to give the title product as a solid: HRMS (ES+): 502.2484 (M+H); 1H NMR (400 MHz, CDCl3) δ 9.35 (br s, 3H), 7.2 (m, 2H), 6.9 (t, J=9 Hz, 1H), 5.34 (br s, 1H), 4.8 (d, J=14 Hz, 1H), 4.5 (m, 21H), 4.5 (m, 2H), 3.3 (d, J=14 Hz, 1H), 3.0 (s, 3H), 2.98, (s, 3H), 2.96 (s, 3H), 2.2 (s, 3H), 2.0 (m, 2H), 1.9 (m, 1H), 1.7 (s, 2H), 1.12 (s, 3H), 0.83 (s, 3H).

Workup

  1. washwashed with 10 mL each of saturated NaHCO3 solution, H2O, and brine
  2. dry with materialdried over Na2SO4
  3. concentrationConcentration
  4. customgave a crude title product which
  5. washwas purifried by preparative reverse phase chromatography (gradient elution 0.1% AcOH in water/acetonitrile)

Sources & evidence

ORD record
ord-928e905b2d12476ba8e964a472856609
Source dataset
uspto-grants-2013_08
Patent number
US08513234B2

Reaction notes

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