Hydrochloric Acid → HCID 54742800, compound

HRID 1920704Notes

Reaction equation

HRID 1920704 reaction equation
[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:17])=[C:11](F)[C:12]=3[O:14][CH3:15])[C:7](=[O:18])[C:6]3[C:19]([OH:25])=[C:20]([C:22]([NH2:24])=[O:23])[S:21][C:5]2=3)[CH2:3][CH2:2]1.C1(N2C3C(=CC(F)=C(F)C=3OC)C(=O)C(C(OCC)=O)=C2S)CC1.C1(N2C3C(=CC(F)=C(F)C=3)C(=O)C3C(O)=C(C(N)=O)SC2=3)CC1.[NH:73]1[CH2:77][CH2:76][C@@H:75]([C:78]([NH2:81])([CH3:80])[CH3:79])[CH2:74]1.Cl>N1C=CC=CC=1.CO>[NH2:81][C:78]([C@@H:75]1[CH2:76][CH2:77][N:73]([C:11]2[C:12]([O:14][CH3:15])=[C:13]3[C:8]([C:7](=[O:18])[C:6]4[C:19]([OH:25])=[C:20]([C:22]([NH2:24])=[O:23])[S:21][C:5]=4[N:4]3[CH:1]3[CH2:3][CH2:2]3)=[CH:9][C:10]=2[F:17])[CH2:74]1)([CH3:80])[CH3:79]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 54123383HCID 54123383, compoundHCID 59526822HCID 59526822, compound2×HCID 66718494HCID 66718494, compoundHCID 178470122HCID 178470122, compound

Product 1

HCID 54742800HCID 54742800, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1049PyridineSolvent

Conditions

Temperature
100 °C

Procedure

The starting material, 9-cyclopropyl-6,7-difluoro-3-hydroxyl-8-methoxy-4-oxo-4,9-dihydrothieno[2,3-b]quinoline-2-carboxamide, is prepared from ethyl 1-cyclopropyl-6,7-difluoro-2-mercapto-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate. (See US 2008071086, and Hashimoto, et al., 2007) using a procedure analogous to that describing the preparation of 9-cyclopropyl-6,7-difluoro-3-hydroxyl-4-oxo-4,9-dihydrothieno[2,3-b]quinoline-2-carboxamide. ((Chiba, et al., JP 03-223289) 1H NMR: δ 0.98-1.03 (m, 2H), 1.24-1.31 (m, 2H), 3.86-3.93 (m, 1H), 4.04 (d, J=1.5 Hz, 3H), 7.88 (dd, J=10.0 Hz, 8.5 Hz, 1H). 19F NMR: δ −145.5 (d, J=22.5 Hz, 1F), −139.4 (d, J=22.5 Hz, 1F). LCMS: m/z calcd for C16H12F2N2O4S ([M]+) 366. found ([M+H]+) 367. The title compound is prepared as follows. (R)-2-(Pyrrolidin-3-yl)propan-2-amine (175 mg, 1.4 mmol) is added to a mixture of 9-cyclopropyl-6,7-difluoro-3-hydroxyl-8-methoxy-4-oxo-4,9-dihydrothieno[2,3-b]quinoline-2-carboxamide (100 mg, 0.3 mmol) in pyridine (9 mL). The reaction mixture is heated at 100° C. for 24 h, cooled to rt, and evaporated under reduced pressure. The resulting residue is purified by preparative HPLC using mass-based fraction collection to provide the desired mass only fractions. The fractions containing product were combined and lyophilized. The resulting solid was treated with a solution of 1.25 M HCl in methanol (3 mL), evaporated, and triturated with diethyl ether. This step was repeated three times. The solid was dissolved in water and lyophilized to afford the desired product (40 mg, 29%, HCl salt).

Workup

  1. customThe title compound is prepared
  2. temperaturecooled to rt
  3. customevaporated under reduced pressure
  4. customThe resulting residue is purified by preparative HPLC
  5. customfraction collection
  6. customto provide the desired mass
  7. additionThe fractions containing product
  8. customevaporated
  9. customtriturated with diethyl ether
  10. dissolutionThe solid was dissolved in water

Sources & evidence

ORD record
ord-cb758684407d4926be0a68fe7c920e01
Source dataset
uspto-grants-2012_05
Patent number
US08173636B2

Reaction notes

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