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

HRID 1467368Notes

Reaction equation

HRID 1467368 reaction equation
Cl.[NH2:2][C:3]1[C:4]2[C:14]([O:15][CH2:16][C:17]3([NH2:22])[CH2:21][CH2:20][CH2:19][CH2:18]3)=[CH:13][CH:12]=[CH:11][C:5]=2[NH:6][S:7](=[O:10])(=[O:9])[N:8]=1.C(N(CC)CC)C.[CH3:30][NH:31][C:32]1[CH:33]=[C:34]([CH:38]=[CH:39][N:40]=1)[C:35](O)=[O:36].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[NH2:2][C:3]1[C:4]2[C:14]([O:15][CH2:16][C:17]3([NH:22][C:35](=[O:36])[C:34]4[CH:38]=[CH:39][N:40]=[C:32]([NH:31][CH3:30])[CH:33]=4)[CH2:21][CH2:20][CH2:19][CH2:18]3)=[CH:13][CH:12]=[CH:11][C:5]=2[NH:6][S:7](=[O:10])(=[O:9])[N:8]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 64842352-(Methylamino)pyridine-4-carboxylic acidHCID 867301294-amino-5-((1-aminocyclopentyl)methoxy)-1H-benzo[c][1,2,6]thiadiazine 2,2-dioxide hydrochloride

Product 1

HCID 85468760N-(1-(((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)methyl)cyclopentyl)-2-(methylamino)isonicotinamideYield 34%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred suspension of 4-amino-5-((1-aminocyclopentyl)methoxy)-1H-benzo[c][1,2,6]thiadiazine 2,2-dioxide hydrochloride (200 mg, 0.577 mmol) in DMF (5 mL) was added triethylamine (0.32 mL, 2.31 mmol). After being stirred at room temperature for 10 min., a mixture of 2-(methylamino)isonicotinic acid (88 mg, 0.577 mmol), EDCI (122 mg, 0.635 mmol) and HOBt (86 mg, 0.635 mmol) in 10 ml of DMF were added, and the reaction mixture was then stirred at room temperature overnight and at 55° C. for 2 hrs. The resulting solution was purified by preparative HPLC (10-90% CH3CN in water). The clean fractions were collected and re-crystallized from ethanol/water, dried at 60° C. under vacuum to provide the title compound (87 mg) in 34% yield. 1H NMR (400 MHz, DMSO-d6) δ 1.62-1.84 (m, 6H), 2.15-2.21 (m, 2H), 2.76 (J=4.8 Hz, 3H), 4.40 (s, 2H), 6.59-6.64 (m, 3H), 6.70-6.72 (m, 1H), 6.77 (d, J=8.0 Hz, 1H), 7.43 (t, J=8.8 Hz, 1H), 7.88 (s, 1H), 8.00 (d, J=5.2 Hz, 1H), 8.33 (s, 1H), 8.38 (s, 1H), 10.97 (s, 1H). MS 445 (MH+).

Workup

  1. additionwere added
  2. stirringthe reaction mixture was then stirred at room temperature overnight and at 55° C. for 2 hrs
  3. customThe resulting solution was purified by preparative HPLC (10-90% CH3CN in water)
  4. customThe clean fractions were collected
  5. customre-crystallized from ethanol/water
  6. customdried at 60° C. under vacuum

Sources & evidence

ORD record
ord-a6b4832d96084e0d945b6751df1c9f1a
Source dataset
uspto-grants-2015_04
Patent number
US09000151B2

Reaction notes

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