Hydrochloric Acid → HCID 66715634, compound

HRID 2271838Notes

Reaction equation

HRID 2271838 reaction equation
[CH:1]1([C:4]([C:6]2[CH:7]=[N:8][C:9]3[C:14]([C:15]=2[NH:16][C:17]2[CH:18]=[CH:19][C:20]([N:23]4[CH2:27][CH2:26][CH:25]([N:28](C)[C:29](=O)OC(C)(C)C)[CH2:24]4)=[N:21][CH:22]=2)=[CH:13][C:12]([C:37]2[CH:42]=[C:41]([Cl:43])[C:40]([OH:44])=[C:39]([Cl:45])[CH:38]=2)=[CH:11][CH:10]=3)=[O:5])[CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O.[ClH:53]>C1COCC1>[ClH:43].[ClH:53].[ClH:43].[CH:1]1([C:4]([C:6]2[CH:7]=[N:8][C:9]3[C:14]([C:15]=2[NH:16][C:17]2[CH:22]=[N:21][C:20]([N:23]4[CH2:27][CH2:26][CH:25]([NH:28][CH3:29])[CH2:24]4)=[CH:19][CH:18]=2)=[CH:13][C:12]([C:37]2[CH:38]=[C:39]([Cl:45])[C:40]([OH:44])=[C:41]([Cl:43])[CH:42]=2)=[CH:11][CH:10]=3)=[O:5])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 86692970Tert-butyl (1-(5-((3-(cyclopropanecarbonyl)-6-(3,5-dichloro-4-hydroxyphenyl)quinolin-4-yl)amino)pyridin-2-yl)pyrrolidin-3-yl)(methyl)carbamate

Product 1

HCID 66715634HCID 66715634, compoundYield 40.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of tert-butyl (1-(5-((3-(cyclopropanecarbonyl)-6-(3,5-dichloro-4-hydroxyphenyl)quinolin-4-yl)amino)pyridin-2-yl)pyrrolidin-3-yl)(methyl)carbamate (90 mg, 0.14 mmol) in THF (3 mL) was added TFA (2 mL). The reaction mixture was heated at 65° C. for 16 h, cooled to room temperature and concentrated. The resultant residue was purified by preparative HPLC (C18 silica, 10-90% acetonitrile/water with 0.05% TFA). The residue was dissolved in methanol (8 mL) and HCl (6 M in water, 1.0 mL, 6 mmol) was added. The resultant solution was concentrated to give the desired product (12.3 mg, 13%) as an orange solid. 1H NMR (500 MHz, MeOD) δ 9.37 (s, 1H), 8.31-8.19 (m, 3H), 8.05 (d, J=8.8 Hz, 1H), 7.87 (dd, J=9.3, 2.7 Hz, 1H), 7.44 (s, 2H), 7.05 (d, J=9.3 Hz, 1H), 4.12-4.01 (m, 2H), 3.93-3.81 (m, 2H), 3.80-3.71 (m, 1H), 2.88-2.79 (m, 1H), 2.83 (s, 3H), 2.69-2.58 (m, 1H), 2.43-2.32 (m, 1H), 1.26-1.18 (m, 4H). ESI MS m/z 548 [C29H27Cl2N5O2+H]+; HPLC 95.9% (AUC), tR=10.31 min.

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated
  3. customThe resultant residue was purified by preparative HPLC (C18 silica, 10-90% acetonitrile/water with 0.05% TFA)
  4. dissolutionThe residue was dissolved in methanol (8 mL)
  5. concentrationThe resultant solution was concentrated

Sources & evidence

ORD record
ord-2bcc3b8e97b940af872dee3132cce4fe
Source dataset
uspto-grants-2015_09
Patent number
US09120749B2

Reaction notes

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