Triethylamine → N-[17-[2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yloxy]-2,14-dioxo-3,15-diazatricyclo[13.3.0.04,6]octadec-7-ene-4-carbonyl]-(cyclopropyl)sulfonamide

HRID 1669583Notes

Reaction equation

HRID 1669583 reaction equation
[CH:1]([C:4]1[N:5]=[C:6]([C:9]2[CH:18]=[C:17]([O:19][CH:20]3[CH2:37][CH:36]4[N:22]([C:23](=[O:48])[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH:29]=[CH:30][CH:31]5[C:33]([C:39]([NH:41][S:42]([CH:45]6[CH2:47][CH2:46]6)(=[O:44])=[O:43])=[O:40])([NH:34][C:35]4=[O:38])[CH2:32]5)[CH2:21]3)[C:16]3[C:11](=[CH:12][C:13]([O:49][CH3:50])=[CH:14][CH:15]=3)[N:10]=2)[S:7][CH:8]=1)([CH3:3])[CH3:2].[CH:51](C1C=C(C(C)C)C=C(C(C)C)C=1S(NN)(=O)=O)(C)C.C(N(CC)CC)C>CO>[CH:1]([C:4]1[N:5]=[C:6]([C:9]2[CH:18]=[C:17]([O:19][CH:20]3[CH2:37][CH:36]4[N:22]([C:23](=[O:48])[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH:29]=[CH:30][CH:31]5[C:33]([C:39]([NH:41][S:42]([CH:45]6[CH2:47][CH2:46]6)(=[O:44])=[O:43])=[O:40])([NH:34][C:35]4=[O:38])[CH2:32]5)[CH2:21]3)[C:16]3[C:11](=[C:12]([CH3:51])[C:13]([O:49][CH3:50])=[CH:14][CH:15]=3)[N:10]=2)[S:7][CH:8]=1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 3593332,4,6-TriisopropylbenzenesulphonohydrazideHCID 67317849N-[17-[2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin-4-yloxy]-2,14-dioxo-3,15-diazatricyclo[13.3.0.04,6]octadec-7-ene-4-carbonyl]-(cyclopropyl)sulfonamide

Product 1

HCID 67319209N-[17-[2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yloxy]-2,14-dioxo-3,15-diazatricyclo[13.3.0.04,6]octadec-7-ene-4-carbonyl]-(cyclopropyl)sulfonamideYield 6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of olefin N-[17-[2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin-4-yloxy]-2,14-dioxo-3,15-diazatricyclo[13.3.0.04,6]octadec-7-ene-4-carbonyl](cyclopropyl)-sulfonamide (63, 100 mg, 0.139 mmole) in MeOH (3.0 mL) heated at 80° C., was added 2,4,6-triisopropylbenzene sulfonohydrazide (TrisNHNH2) and triethylamine portion wise over several hours. Then, the reaction mixture was concentrated under reduced pressure. The residue was partitioned between CH2Cl2 and a saturated solution of NaHCO3, successively washed with HCl 1N and brine, dried (MgSO4), filtered and evaporated. Purification by flash chromatography (gradient of AcOEt/CH2Cl2, 0:1 to 1:9) followed by recrystallization from isopropylether/petroleum ether, and then preparative HPLC afforded 6 mg (6%) of the title product (59) as a white powder: m/z=724 (M+H)+. 1H NMR (CDCl3): 0.90-1.70 (m, 21H), 1.95-2.03 (m, 2H), 2.25-2.35 (m, 2H), 2.63-2.68 (m, 2H), 2.99 (m, 1H), 3.22 (m, 1H), 3.41 (m, 1H), 3.96 (m, 5H), 4.15 (d, J=15 Hz, 1H), 4.60 (t, J=7.9 Hz, 1H), 5.53 (m, 1H), 6.57 (s, 1H), 7.05 (s, 1H), 7.12 (dd, J=2.5 Hz, 9.1 Hz, 1H), 7.38 (d, J=2.5 Hz, 1H), 7.56 (s, 1H), 7.93 (d, J=9.1 Hz, 1H), 10.8 (br s, 1H).

Workup

  1. concentrationThen, the reaction mixture was concentrated under reduced pressure
  2. customThe residue was partitioned between CH2Cl2
  3. washa saturated solution of NaHCO3, successively washed with HCl 1N and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customPurification by flash chromatography (gradient of AcOEt/CH2Cl2, 0:1 to 1:9)
  8. customfollowed by recrystallization from isopropylether/petroleum ether

Sources & evidence

ORD record
ord-832e20b78e09405b85504eff69ebf5c4
Source dataset
uspto-grants-2011_08
Patent number
US07989471B2

Reaction notes

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