Hydrochloric Acid → HCID 178478722, compound

HRID 2271826Notes

Reaction equation

HRID 2271826 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]=[N:19][N:20]([C@H:22]4[CH2:27][CH2:26][C@H:25]([NH:28]C(=O)OC(C)(C)C)[CH2:24][CH2:23]4)[CH:21]=2)=[CH:13][C:12]([C:36]2[CH:41]=[C:40]([Cl:42])[C:39]([OH:43])=[C:38]([Cl:44])[CH:37]=2)=[CH:11][CH:10]=3)=[O:5])[CH2:3][CH2:2]1.FC(F)(F)C(O)=O.[ClH:52]>C1COCC1>[ClH:42].[ClH:52].[NH2:28][C@H:25]1[CH2:26][CH2:27][C@H:22]([N:20]2[CH:21]=[C:17]([NH:16][C:15]3[C:14]4[C:9](=[CH:10][CH:11]=[C:12]([C:36]5[CH:37]=[C:38]([Cl:44])[C:39]([OH:43])=[C:40]([Cl:42])[CH:41]=5)[CH:13]=4)[N:8]=[CH:7][C:6]=3[C:4]([CH:1]3[CH2:2][CH2:3]3)=[O:5])[CH:18]=[N:19]2)[CH2:23][CH2:24]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 178453982HCID 178453982, compound

Product 1

HCID 178478722HCID 178478722, compoundYield 101.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl (trans-4-(4-((3-(cyclopropanecarbonyl)-6-(3,5-dichloro-4-hydroxyphenyl)quinolin-4-yl)amino)-1H-pyrazol-1-yl)cyclohexyl)carbamate (23 mg, 0.036 mmol) in THF (3 mL) was added trifluoroacetic acid (2 mL). The resultant mixture was heated at 65° C. for 16 h. The mixture was then 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 (5 mL) and HCl (2 M in diethyl ether, 2.0 mL, 4 mmol) was added. The resultant solution was concentrated to give the desired product (11.1 mg, 50%) as a yellow solid. 1H NMR (500 MHz, MeOD) δ 9.50 (br s, 1H), 8.22 (d, J=8.7 Hz, 1H), 8.13 (br s, 1H), 8.00 (d, J=8.7 Hz, 2H), 7.63 (s, 2H), 7.36 (br s, 2H), 4.35-4.31 (m, 1H), 3.26-3.17 (m, 1H), 2.97-2.89 (br s, 1H), 2.28-2.16 (m, 4H), 2.04-1.91 (m, 2H), 1.70-1.58 (m, 2H), 1.33-1.20 (m, 4H). ESI MS m/z 536 [C28H27Cl2N5O2+H]+; HPLC 96.0% (AUC), tR=11.44 min.

Workup

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

Sources & evidence

ORD record
ord-d9373ed447354a1fa4bdb6125b02e1c5
Source dataset
uspto-grants-2015_09
Patent number
US09120749B2

Reaction notes

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