Dimethylformamide → N-(1-(((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)methyl)cyclopentyl)-2-methylisonicotinamide

HRID 1467367Notes

Reaction equation

HRID 1467367 reaction equation
Cl.[NH:2]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[CH:5]=[N:4][S:3]1(=[O:13])=[O:12].C([N:16](CC)CC)C.[CH3:21][C:22]1[CH:27]=[C:26]([C:28]([OH:30])=O)[CH:25]=[CH:24][N:23]=1.CCN=C=NCCCN(C)C.Cl.[CH:43]1[CH:48]=[C:47]2N=N[N:51](O)[C:46]2=[CH:45]C=1.O.CN([CH:57]=[O:58])C>>[NH2:16][C:5]1[C:6]2[C:11]([O:58][CH2:57][C:46]3([NH:51][C:28](=[O:30])[C:26]4[CH:25]=[CH:24][N:23]=[C:22]([CH3:21])[CH:27]=4)[CH2:45][CH2:43][CH2:48][CH2:47]3)=[CH:10][CH:9]=[CH:8][C:7]=2[NH:2][S:3](=[O:12])(=[O:13])[N:4]=1

Participants

7

Reactant 6

HCID 6228Dimethylformamide2×HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27628212-Methylpyridine-4-carboxylic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 86730131HCID 86730131, compound

Product 1

HCID 85468759N-(1-(((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)methyl)cyclopentyl)-2-methylisonicotinamideYield 40%

Procedure

To a solution of 4-amino-5-(1-aminocyclopentyl)methoxy)-1H-benzo[c][1,2,6]thiadiazine-2,2-dioxide hydrochloride (252 mg, 0.72 mmol) in DMF (7 mL) was added triethylamine (202 uL, 1.45 mmol), followed by a solution of 2-methylpyridine-4-carboxylic acid (99 mg, 0.72 mmol), EDCI HCl (138 mg, 0.72 mmol), and HOBt hydrate (110 mg, 0.72 mmol) in DMF (5 mL). The reaction was stirred at room temperature for 24 h, and the resulting solution was purified by HPLC (10-90% acetonitrile in water). After removal of the solvent, the residue was suspended in an aqueous solution of NaHCO3 (208 mg in 3 mL of water) and heated to 95° C. After complete dissolution, the mixture was cooled to 0° C., neutralized with 1N HCl, and the resulting precipitate was collected by vacuum filtration to provide N-(1-(((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)methyl)cyclopentyl)-2-methylisonicotinamide (124.1 mg, 40%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 1.66 (m, 2H), 1.74 (m, 2H), 1.82 (m, 2H), 2.19 (m, 2H), 2.50 (s, 3H), 4.42 (s, 2H), 6.59 (d, J=8.4 Hz, 1H), 6.77 (d, J=8.4 Hz, 1H), 7.42 (t, J=8.4 Hz, 1H), 7.44 (m, 1H), 7.51 (s, 1H), 7.83 (br s, 1H), 8.40 (br s, 1H), 8.49 (s, 1H), 8.51 (d, J=5.1 Hz, 1H), 10.95 (br s, 1H). MS 430 (MH+).

Workup

  1. customthe resulting solution was purified by HPLC (10-90% acetonitrile in water)
  2. customAfter removal of the solvent
  3. temperatureheated to 95° C
  4. dissolutionAfter complete dissolution
  5. temperaturethe mixture was cooled to 0° C.
  6. filtrationthe resulting precipitate was collected by vacuum filtration

Sources & evidence

ORD record
ord-b55a60e5373347c390c4ff64a37a07e8
Source dataset
uspto-grants-2015_04
Patent number
US09000151B2

Reaction notes

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