Dichloromethane → HCID 59843013, compound

HRID 1878784Notes

Reaction equation

HRID 1878784 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5](=[O:23])[N:6]([CH2:8][CH2:9][O:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=3)[N:14]=[CH:13][CH:12]=2)[N:7]=1.Cl.[NH2:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C([O-])([O-])=O.[Na+].[Na+].ClCCl>COCCOC>[NH2:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([C:2]2[CH:3]=[CH:4][C:5](=[O:23])[N:6]([CH2:8][CH2:9][O:10][C:11]3[C:20]4[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=4)[N:14]=[CH:13][CH:12]=3)[N:7]=2)=[CH:29][CH:28]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 27343114-Aminomethylphenylboronic acid hydrochlorideHCID 598430126-chloro-2-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridazin-3(2H)-one

Product 1

HCID 59843013HCID 59843013, compound

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A suspension of 6-chloro-2-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridazin-3(2H)-one (1250 mg, 3768 μmol), (4-aminomethylphenyl)boronic acid, hydrochloride (1412 mg, 7536 μmol), Na2CO3 (7536 μL, 15071 μmol) [2M], and [1,1′-bis(diphenylphosphino)ferrocene]dichloride palladium(II) complex with dichloromethane (276 mg, 377 μmol) in DME (2 mL) was sparged with argon for 5 minutes then heated to 85° C. for 4 hours. The reaction was then partitioned between DCM (50 mL) and 1 M NaOH (20 mL). The organic was dried over MgSO4, concentrated onto dry silica (10 g) then purified on silica (40 g) eluting with 0>5% MeOH/DCM. The product was isolated as an off white solid from ACN. MS (ESI pos. ion) m/z: 403 (MH+); calc'd for C23H22N4O3: 402. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.76 (s, 2 H) 3.87 (s, 3 H) 4.67 (s, 4 H) 6.95 (d, J=5.28 Hz, 1 H) 7.01 (dd, J=9.00, 2.54 Hz, 1 H) 7.08 (d, J=9.78 Hz, 1 H) 7.27 (d, J=2.35 Hz, 1 H) 7.41 (d, J=8.22 Hz, 2 H) 7.78 (d, J=8.41 Hz, 2 H) 7.90 (d, J=9.19 Hz, 1 H) 8.03 (d, J=9.78 Hz, 1 H) 8.62 (d, J=5.28 Hz, 1 H).

Workup

  1. customwas sparged with argon for 5 minutes
  2. customThe reaction was then partitioned between DCM (50 mL) and 1 M NaOH (20 mL)
  3. dry with materialThe organic was dried over MgSO4
  4. concentrationconcentrated onto dry silica (10 g)
  5. customthen purified on silica (40 g)
  6. washeluting with 0>5% MeOH/DCM
  7. customThe product was isolated as an off white solid from ACN

Sources & evidence

ORD record
ord-9e81f6371e5f4d27bc5bcb119fca03a8
Source dataset
uspto-grants-2012_11
Patent number
US08314087B2

Reaction notes

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