Triethylamine → HCID 136124352, compound

HRID 601414Notes

Reaction equation

HRID 601414 reaction equation
N[C:2]1[CH:30]=CC2NC(C3C(=O)N(CCC(C)C)C4C(C=3O)=CC=CN=4)=NS(=O)(=O)C=2[CH:3]=1.[OH:31][C:32]1[C:41]2[C:36](=[N:37][CH:38]=[CH:39][CH:40]=2)[N:35]([CH2:42][CH2:43][CH:44]([CH3:46])[CH3:45])[C:34](=[O:47])[C:33]=1[C:48]1[NH:53][C:52]2[CH:54]=[CH:55][C:56]([NH:58][S:59]([N:62]3[CH2:66]CC(NC(=O)OC(C)(C)C)[CH2:63]3)(=[O:61])=[O:60])=[CH:57][C:51]=2[S:50](=[O:76])(=[O:75])[N:49]=1.C(N(CC)CC)C>ClCCl>[OH:31][C:32]1[C:41]2[C:36](=[N:37][CH:38]=[CH:39][CH:40]=2)[N:35]([CH2:42][CH2:43][CH:44]([CH3:45])[CH3:46])[C:34](=[O:47])[C:33]=1[C:48]1[NH:53][C:52]2[CH:54]=[CH:55][C:56]([NH:58][S:59]([N:62]3[CH2:66][CH2:30][CH2:2][CH2:3][CH2:63]3)(=[O:61])=[O:60])=[CH:57][C:51]=2[S:50](=[O:75])(=[O:76])[N:49]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1354307103-(7-Amino-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1-(3-methylbutyl)-1,8-naphthyridin-2(1H)-oneHCID 136358517HCID 136358517, compound

Product 1

HCID 136124352HCID 136124352, compoundYield 371.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of the product of Example 205 (2 mg, 0.1 ml), the product of Example 451A (17 mg, 0.1 mmol) and triethylamine (0.1 mL) in dichloromethane (2 mL) was stirred for 18 hours at 25° C., diluted with dichloromethane (25 mL) and washed with 1 N HCl and brine. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The product was purified by reverse phase preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size) using a gradient of 10% to 100% acetonitrile/10 mM ammonium acetate in water over 8 minutes (10 minutes run time) at a flow rate of 40 mL/min to provide the title compound (10 mg). 1H NMR (300 MHz, DMSO-d6) δ 0.98 (d, J=6.62 Hz, 6 H) 1.43 (s, 6 H) 1.57 (m, 2 H) 1.69 (m, 1 H) 3.14 (s, 4 H) 4.49 (m, 2 H) 7.51 (m, 1 H) 7.53 (s, 1 H) 7.60 (d, J=2.21 Hz, 1 H) 7.72 (d, J=8.82 Hz, 1 H) 8.56 (dd, J=8.09, 1.84 Hz, 1 H) 8.90 (dd, J=4.78, 1.84 Hz, 1 H) 10.47 (s, 1 H) 14.06 (s, 1 H) 15.05 (s, 1 H). MS (ESI−) m/z 573 (M−H)−.

Workup

  1. washwashed with 1 N HCl and brine
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe product was purified by reverse phase preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size)
  6. customover 8 minutes
  7. custom(10 minutes run time)

Sources & evidence

ORD record
ord-4a39008a0669438db297293bdd5b3b85
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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