Triethylamine → 1-(6-(4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazin-5-yloxy)hexyl)-3-(4-methoxybenzyl)urea

HRID 711922

Reaction equation

HRID 711922 reaction equation
[Cl-].[NH2:2][C:3]1[C:4]2[C:14]([O:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][NH3+:22])=[CH:13][CH:12]=[CH:11][C:5]=2[NH:6][S:7](=[O:10])(=[O:9])[N:8]=1.CCN(CC)CC.[N:30]([CH2:33][C:34]1[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=1)=[C:31]=[O:32]>C(Cl)Cl>[NH2:2][C:3]1[C:4]2[C:14]([O:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][NH:22][C:31]([NH:30][CH2:33][C:34]3[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=3)=[O:32])=[CH:13][CH:12]=[CH:11][C:5]=2[NH:6][S:7](=[O:10])(=[O:9])[N:8]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 187910Isocyanic acid, p-methoxybenzyl-HCID 667460276-(4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazin-5-yloxy)hexan-1-aminium chloride

Product 1

HCID 568326631-(6-(4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazin-5-yloxy)hexyl)-3-(4-methoxybenzyl)ureaYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 6-(4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazin-5-yloxy)hexan-1-aminium chloride (166 mmol, 52 mg) (Example 280) in dry DCM (6 mL) was successively added Et3N (332 mmol, 46 μL) and 1-(isocyanatomethyl)-4-methoxybenzene (183 mmol, 26 μL). The reaction was stirred for 48 hours at room temperature then concentrated in vacuo. The residue was washed with water, dried, then purified on silica gel (20% to 100% EtOAc in hexanes) to give the desired product (64 mg, 81.0% yield). 1H NMR (400 MHz, DMSO-d6) δ 1.296 (m, 2H), 1.371 (m, 4H), 1.791 (pentet, J=8 Hz, 2H), 2.980 (q, J=6 Hz, 2H), 3.695 (s, 3H), 4.086 (d, J=6 Hz, 2H), 4.131 (t, J=6 Hz, 2H), 5.836 (br. t, J=5 Hz, 1H), 6.141 (br. t, J=6 Hz, 1H), 6.585 (d, J=8 Hz, 1H), 6.727 (d, J=8 Hz, 1H), 6.840 (d, J=9 Hz, 2H), 7.137 (d, J=9 Hz, 2H), 7.433 (t, J=8 Hz, 1H), 7.803 (br. s, 1H), 8.321 (br. s, 1H), 10.926 (s, 1H). MS 476 (MH+).

Workup

  1. concentrationthen concentrated in vacuo
  2. washThe residue was washed with water
  3. customdried
  4. custompurified on silica gel (20% to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-5c657f71655c42dd9bddc7fa01279368
Source dataset
uspto-grants-2015_11
Patent number
US09181276B2

Linked notes

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