Hydrochloric Acid → HCID 46940346, compound

HRID 1920701Notes

Reaction equation

HRID 1920701 reaction equation
[F:1][CH2:2][CH2:3][NH:4][C@H:5]([C@@H:7]1[CH2:11][CH2:10][NH:9][CH2:8]1)[CH3:6].C(N(C(C)C)CC)(C)C.[CH:21]1([N:24]2[C:33]3[C:28](=[CH:29][C:30]([F:37])=[C:31](F)[C:32]=3[O:34][CH3:35])[C:27](=[O:38])[C:26]3[C:39]([OH:44])=[C:40]([C:42]#[N:43])[S:41][C:25]2=3)[CH2:23][CH2:22]1.Cl>CS(C)=O.CO>[CH:21]1([N:24]2[C:33]3[C:28](=[CH:29][C:30]([F:37])=[C:31]([N:9]4[CH2:10][CH2:11][C@@H:7]([C@@H:5]([NH:4][CH2:3][CH2:2][F:1])[CH3:6])[CH2:8]4)[C:32]=3[O:34][CH3:35])[C:27](=[O:38])[C:26]3[C:39]([OH:44])=[C:40]([C:42]#[N:43])[S:41][C:25]2=3)[CH2:22][CH2:23]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 59526799HCID 59526799, compoundHCID 59526811HCID 59526811, compound

Product 1

HCID 46940346HCID 46940346, compoundYield 30.7%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent

Conditions

Temperature
110 °C

Procedure

2-Fluoro-N—((S)-1-((R)-pyrrolidin-3-yl)ethyl)ethanamine (0.14 g, 0.87 mmol) and diisopropylethylamine (0.38 mL, 2.18 mmol) are added to a mixture of 9-cyclopropyl-6,7-difluoro-3-hydroxyl-8-methoxy-4-oxo-4,9-dihydrothieno[2,3-b]quinoline-2-carbonitrile (0.15 g, 0.44 mmol) in DMSO (2 mL). The reaction mixture is heated at 110° C. for 18 h, and cooled to rt. The resulting solution 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 brown solid was dissolved in water and lyophilized to afford the desired product (66.1 mg, 29%, HCl salt) as a brown solid.

Workup

  1. temperaturecooled to rt
  2. customThe resulting solution is purified by preparative HPLC
  3. customfraction collection
  4. customto provide the desired mass
  5. additionThe fractions containing product
  6. customevaporated
  7. customtriturated with diethyl ether
  8. dissolutionThe brown solid was dissolved in water

Sources & evidence

ORD record
ord-1fdf7bb4c0924a19aa67d3ab8aadd9d7
Source dataset
uspto-grants-2012_05
Patent number
US08173636B2

Reaction notes

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