Hydrochloric Acid → HCID 131732650, compound

HRID 882288Notes

Reaction equation

HRID 882288 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:15]=[CH:16][C:17]([C:20]([N:22]4[CH2:27][CH2:26][CH:25]([NH:28]C(=O)OC(C)(C)C)[CH2:24][CH2:23]4)=[O:21])=[N:18][CH:19]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:36][C:37]2[CH:42]=[CH:41][C:40]([C:43]#[N:44])=[CH:39][N:38]=2)[CH2:6][C@@H:5]1[CH3:45])(=[O:3])[CH3:2].C(O)(C(F)(F)F)=O.[ClH:53]>C(Cl)Cl.CO.C(OCC)C>[ClH:53].[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:19]=[N:18][C:17]([C:20]([N:22]4[CH2:27][CH2:26][CH:25]([NH2:28])[CH2:24][CH2:23]4)=[O:21])=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:36][C:37]2[CH:42]=[CH:41][C:40]([C:43]#[N:44])=[CH:39][N:38]=2)[CH2:6][C@@H:5]1[CH3:45])(=[O:3])[CH3:2]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 86709435HCID 86709435, compound

Product 1

HCID 131732650HCID 131732650, compoundYield 8.59%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

tert-Butyl (1-(5-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)picolinoyl)piperidin-4-yl)carbamate (for a preparation see Intermediate 43) (0.258 ml, 0.313 mmol) was dissolved in anhydrous DCM (4 ml). TFA (1 ml, 12.98 mmol) was added and the reaction mixture which was stirred under nitrogen at r.t. for 8 h. The reaction mixture was concentrated in vacuo and loaded onto a SCX cartridge (5 g, pre-conditioned with MeOH). The cartridge was washed with MeOH (40 ml) and eluted with ammonia in MeOH (2M). The methanolic ammonia fractions were concentrated to give an orange oil. The oil was further purified by chromatography on a silica cartridge (10 g), eluting with a MeOH/DCM gradient (2-12%, over 120 mls) followed by 10% of 2M NH3 in MeOH/DCM for 120 mls to give a pale orange solid. The solid was re-dissolved in MeOH (1 ml) and 1.1 equivalents of 1M hydrogen chloride in diethyl ether were added. The mixture was triturated with diethyl ether to give 6-(((2S,4R)-1-acetyl-6-(6-(4-aminopiperidine-1-carbonyl)pyridin-3-yl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile, hydrochloride (19 mg, 0.030 mmol, 8.59% yield) as an orange solid. LCMS (Formate, 2 min), Rt=0.60 min, MH+=510.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. washThe cartridge was washed with MeOH (40 ml)
  3. washeluted with ammonia in MeOH (2M)
  4. concentrationThe methanolic ammonia fractions were concentrated
  5. customto give an orange oil
  6. customThe oil was further purified by chromatography on a silica cartridge (10 g)
  7. washeluting with a MeOH/DCM gradient (2-12%, over 120 mls)
  8. customto give a pale orange solid
  9. customThe mixture was triturated with diethyl ether

Sources & evidence

ORD record
ord-6ae5c2dde20540e78a8ee1cb9fd01ef7
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

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