Methyl N-(triethylammoniosulfonyl)carbamate → N'-(3-(Benzyloxy)-2-(5-(4-fluorobenzyl)-1,3-oxazol-2-yl)-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)-N,N-dimethylethanediamide

HRID 80700Notes

Reaction equation

HRID 80700 reaction equation
[CH2:1]([O:8][C:9]1[C:29](=[O:30])[N:13]2[CH2:14][CH:15]3[CH2:20][CH2:19][C:18]([NH:21][C:22](=[O:28])[C:23]([N:25]([CH3:27])[CH3:26])=[O:24])([C:12]2=[N:11][C:10]=1[C:31](=[O:44])[NH:32][CH2:33][C:34](=O)[CH2:35][C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=1)[CH2:17][CH2:16]3)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>C1COCC1>[CH2:1]([O:8][C:9]1[C:29](=[O:30])[N:13]2[CH2:14][CH:15]3[CH2:20][CH2:19][C:18]([NH:21][C:22](=[O:28])[C:23]([N:25]([CH3:26])[CH3:27])=[O:24])([C:12]2=[N:11][C:10]=1[C:31]1[O:44][C:34]([CH2:35][C:36]2[CH:37]=[CH:38][C:39]([F:42])=[CH:40][CH:41]=2)=[CH:33][N:32]=1)[CH2:17][CH2:16]3)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 2724994Methyl N-(triethylammoniosulfonyl)carbamateHCID 67960337N'-(3-(Benzyloxy)-2-((3-(4-fluorophenyl)-2-oxopropyl)carbamoyl)-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)-N,N-dimethylethanediamide

Product 1

HCID 67960355N'-(3-(Benzyloxy)-2-(5-(4-fluorobenzyl)-1,3-oxazol-2-yl)-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)-N,N-dimethylethanediamideYield 53.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of N′-(3-(benzyloxy)-2-((3-(4-fluorophenyl)-2-oxopropyl)carbamoyl)-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)-N,N-dimethylethanediamide, Intermediate 16 (125 mg, 0.207 mmol) in THF (8 mL) was added Burgess Reagent (345 mg, 1.450 mmol) and the mixture heated to reflux for 5 h. The mixture was then cooled, concentrated and purified by preparative HPLC to afford the title compound (65 mg, 0.111 mmol, 53.6% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ ppm 9.24 (1H, s), 7.38-7.42 (2H, m), 7.30-7.34 (3H, m), 7.18-7.23 (2H, m), 7.11 (1H, s), 6.99-7.04 (2H, m), 5.38 (2H, s), 4.18 (2H, d, J=3.66 Hz), 4.02 (2H, s), 3.30 (3H, s), 3.03 (3H, s), 2.88-2.96 (2H, m), 2.54 (1H, br. s.), 1.94-2.10 (4H, m), 1.71-1.80 (2H, m). LCMS (M+H)=586.31.

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 5 h
  3. temperatureThe mixture was then cooled
  4. concentrationconcentrated
  5. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-765c4972071a48cd9d41d2271d67bd00
Source dataset
uspto-grants-2014_09
Patent number
US08846659B2

Reaction notes

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