Hydrochloric Acid → 1-(2-[6-Methyl-8-[4-(1-phenyl-1H-pyrazol-3-ylmethyl)-[1,4]diazepan-1-yl]-quinolin-7-yloxy]-acetyl)-azetidine-3-carboxylic Acid

HRID 2063573Notes

Reaction equation

HRID 2063573 reaction equation
C[O:2][C:3]([CH:5]1[CH2:8][N:7]([C:9](=[O:42])[CH2:10][O:11][C:12]2[C:21]([N:22]3[CH2:28][CH2:27][CH2:26][N:25]([CH2:29][C:30]4[CH:34]=[CH:33][N:32]([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)[N:31]=4)[CH2:24][CH2:23]3)=[C:20]3[C:15]([CH:16]=[CH:17][CH:18]=[N:19]3)=[CH:14][C:13]=2[CH3:41])[CH2:6]1)=[O:4].[OH-].[Na+].Cl>C1COCC1>[CH3:41][C:13]1[CH:14]=[C:15]2[C:20](=[C:21]([N:22]3[CH2:28][CH2:27][CH2:26][N:25]([CH2:29][C:30]4[CH:34]=[CH:33][N:32]([C:35]5[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=5)[N:31]=4)[CH2:24][CH2:23]3)[C:12]=1[O:11][CH2:10][C:9]([N:7]1[CH2:6][CH:5]([C:3]([OH:4])=[O:2])[CH2:8]1)=[O:42])[N:19]=[CH:18][CH:17]=[CH:16]2

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 593661781-(2-{6-Methyl-8-[4-(1-phenyl-1H-pyrazol-3-ylmethyl)-[1,4]diazepan-1-yl]-quinolin-7-yloxy}-acetyl)-azetidine-3-carboxylic acid methyl ester

Product 1

HCID 462034121-(2-[6-Methyl-8-[4-(1-phenyl-1H-pyrazol-3-ylmethyl)-[1,4]diazepan-1-yl]-quinolin-7-yloxy]-acetyl)-azetidine-3-carboxylic AcidYield 67.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1-(2-{6-Methyl-8-[4-(1-phenyl-1H-pyrazol-3-ylmethyl)-[1,4]diazepan-1-yl]-quinolin-7-yloxy}-acetyl)-azetidine-3-carboxylic acid methyl ester (70 mg, 0.12 mmol) was hydrolyzed with 2 N NaOH (0.15 mL) in THF (1 ml). After hydrolysis was complete, 2 N HCl (ca. 0.15 mL) was added to bring the pH to 7 and the mixture was extracted with 20% iPrOH in CH2Cl2 (3×10 mL). The combined organic layer was dried over MgSO4 and concentrated. The residue was purified by reverse phase HPLC to afford the title compound (45 mg, 66%) as a light yellow solid. 1H NMR (400 MHz, DMSO) δ 8.75 (d, 1H, J=4.4 Hz), 8.42 (d, 1H, J=2.4 Hz), 8.14 (dd, 1H, J=1.6 and 8.4 Hz), 7.78 (d, 2H, J=8.0 Hz), 7.48-7.42 (m, 3H), 7.35 (q, 1H, J=4.4 Hz), 7.25 (t, 1H, J=7.2 Hz), 6.51 (d, 1H, J=2.8 Hz), 4.77 (s, 2H), 4.40 (t, 1H, J=10.0 Hz), 4.31 (t, 1H, J=6.4 Hz), 4.08 (t, 1H, J=9.2 Hz), 3.97-3.93 (m, 1H), 3.82 (s, 2H), 3.48-3.38 (m, 5H), 2.88 (s, 4H), 2.38 (s, 3H), 1.92 (m, 2H). MS (ES) m/z 555.5 (M+H+).

Workup

  1. customAfter hydrolysis
  2. extractionthe mixture was extracted with 20% iPrOH in CH2Cl2 (3×10 mL)
  3. dry with materialThe combined organic layer was dried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-448a89a79f9d4ff396c276d0c191f341
Source dataset
uspto-grants-2012_10
Patent number
US08288373B2

Reaction notes

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