1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-butyl (NE)-N-[[(8-bromo-4,5-dihydrothieno[3,2-d][1]benzoxepine-2-carbonyl)amino]-methylsulfanylmethylidene]carbamate

HRID 708213Notes

Reaction equation

HRID 708213 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[S:12][C:13]([C:15]([OH:17])=O)=[CH:14][C:10]=3[CH2:9][CH2:8][O:7][C:6]=2[CH:18]=1.CCN=C=NCCCN(C)C.[C:30]([NH:37][C:38](=[NH:41])[S:39][CH3:40])([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[S:12][C:13]([C:15]([N:41]=[C:38]([S:39][CH3:40])[NH:37][C:30]([O:32][C:33]([CH3:34])([CH3:35])[CH3:36])=[O:31])=[O:17])=[CH:14][C:10]=3[CH2:9][CH2:8][O:7][C:6]=2[CH:18]=1

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 579001638-Bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxylic acidHCID 137319820tert-butyl N-[(methylsulfanyl)methanimidoyl]carbamate

Product 1

HCID 178503937tert-butyl (NE)-N-[[(8-bromo-4,5-dihydrothieno[3,2-d][1]benzoxepine-2-carbonyl)amino]-methylsulfanylmethylidene]carbamateYield 67.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture 8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxylic acid (10.0 g, 30.3 mmol), EDCI (7.5 g, 36.4 mmol) in DCM (200 mL) was stirred at room temperature for 10 min, then DMAP (7.39 g, 60.6 mmol) was added by one portion. 10 minutes later, N-Boc-2-Methyl-isothiourea (6.9 g, 36.4 mmol) was added. The reaction mixture was stirred at room temperature overnight. After removal of the solvent, the residue was treated with methanol/water (20 mL, 1:1) to afford 10.2 g of methyl N′-8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carbonyl-N-Boc-carbamimidothioate. Yield: 67%. 1H NMR (CDCl3, 400 MHz): δ12.33 (s, 1H), 7.95-7.51 (m, 2H), 7.35-6.94 (m, 2H), 4.28-4.25 (m, 2H), 3.15-3.30 (m, 2H), 2.52 (s, 3H), 1.51-1.45 (s, 9H). LC-MS: m/z=497 [M+H+]

Workup

  1. customAfter removal of the solvent
  2. additionthe residue was treated with methanol/water (20 mL, 1:1)

Sources & evidence

ORD record
ord-91876d429c434f8ea67305f631aadfc3
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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