Sodium Carbonate → tert-Butyl 2-(3-(4-methylthiophen-2-yl)-6-oxopyridazin-1(6H)-yl)ethylcarbamate

HRID 1878748Notes

Reaction equation

HRID 1878748 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5](=[O:8])[N:4]([CH2:9][CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[N:3]=1.[CH3:19][C:20]1[CH:21]=[C:22](B(O)O)[S:23][CH:24]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:19][C:20]1[CH:21]=[C:22]([C:2]2[CH:7]=[CH:6][C:5](=[O:8])[N:4]([CH2:9][CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[N:3]=2)[S:23][CH:24]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343734-Methylthiophene-2-boronic acidHCID 59843113tert-Butyl 2-(3-chloro-6-oxopyridazin-1(6H)-yl)ethylcarbamate

Product 1

HCID 59843099tert-Butyl 2-(3-(4-methylthiophen-2-yl)-6-oxopyridazin-1(6H)-yl)ethylcarbamate

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of tert-butyl 2-(3-chloro-6-oxopyridazin-1(6H)-yl)ethylcarbamate (2000 mg, 7.31 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (535 mg, 0.731 mmol), and 4-methylthiophen-2-ylboronic acid (2075 mg, 14.6 mmol) in DME (1.6 mL) with Na2CO3 (10.9 mL, 21.9 mmol) [2M] was sparged with argon for 1 min, then heated to 90° C. for 2 h. The mixture was partitioned between CH2Cl2 and 5% NaHCO3, and the organic layer was dried over MgSO4 and dried onto dry silica. The product was purified on 80 g silica eluting with 1>2.5% MeOH/CH2Cl2. MS (ESI pos. ion) m/z (MH+): 336 Calc'd exact mass for C16H21N3O3S: 335. 1H NMR (400 MHz, Chloroform-d) δ ppm 1.40 (s, 9 H) 2.28 (s, 3 H) 3.61 (d, J=5.02 Hz, 2 H) 4.32 (t, J=5.27 Hz, 2 H) 5.11 (br. s., 1 H) 6.91-6.99 (m, 2 H) 7.20 (s, 1 H) 7.55 (d, J=10.04 Hz, 1 H). 13C NMR (101 MHz, Chloroform-d) δ ppm 13.71, 26.35, 37.78, 49.41, 77.33, 121.32, 125.75, 127.40, 127.95, 136.53, 139.01, 153.88, 157.97.

Workup

  1. customwas sparged with argon for 1 min
  2. customThe mixture was partitioned between CH2Cl2 and 5% NaHCO3
  3. dry with materialthe organic layer was dried over MgSO4
  4. customdried onto dry silica
  5. customThe product was purified on 80 g silica eluting with 1>2.5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-e0f58f3ead5b4a29ba693a9afb6a081c
Source dataset
uspto-grants-2012_11
Patent number
US08314087B2

Reaction notes

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