Tetrahydrofuran → HCID 68488561, compound

HRID 1428885Notes

Reaction equation

HRID 1428885 reaction equation
C(=O)([O-])[O-].[K+].[K+].[C:7]1(B(O)O)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH2:16]([O:18][C:19]([C:21]1[CH:22]=[N:23][N:24]([C:26]2[N:35]([CH2:36][O:37][CH2:38][CH2:39][O:40][CH3:41])[C:34](=[O:42])[C:33]3[C:28](=[CH:29][C:30](I)=[CH:31][CH:32]=3)[N:27]=2)[CH:25]=1)=[O:20])[CH3:17].C1COCC1>C(Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl>[CH2:16]([O:18][C:19]([C:21]1[CH:22]=[N:23][N:24]([C:26]2[N:35]([CH2:36][O:37][CH2:38][CH2:39][O:40][CH3:41])[C:34](=[O:42])[C:33]3[C:28](=[CH:29][C:30]([C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=4)=[CH:31][CH:32]=3)[N:27]=2)[CH:25]=1)=[O:20])[CH3:17]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 68486204HCID 68486204, compound

Product 1

HCID 68488561HCID 68488561, compoundYield 85.3%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
80 °C

Procedure

A mixture of potassium carbonate (210 mg 1.52 mmol), phenylboronic acid (156 mg, 1.28 mmol), 1-[7-iodo-3-(2-methoxy-ethoxymethyl)-4-oxo-3,4-dihydro-quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (250 mg, 0.502 mmol), and THF (4.4 ml) was degassed with nitrogen for 10 min in a sealable tube. The dichloromethane adduct of 1,1′-bis(diphenylphosphino)ferrocene]dichloro palladium (48.9 mg, 0.0610 mmol) was added to the reaction mixture and the pressure tube was sealed. The reaction mixture was stirred at 80° C. for 18 h. The reaction mixture was cooled to 23° C., diluted with DCM (15 mL), and filtered. The filtrate was concentrated. The residue was purified by FCC (5-45% EtOAc/hexanes) to yield the titled compound (192 mg, 85%). MS (ESI): mass calcd. for C24H24N4O5, 448.2; m/z found, 449.2 [M+H]+. 1H NMR (400 MHz, DMSO-d6): 8.88 (d, J=0.6 Hz, 1H), 8.30 (d, J=0.6 Hz, 1H), 8.04 (d, J=1.5 Hz, 1H), 8.00 (dd, J=8.3, 1.8 Hz, 1H), 7.88-7.84 (m, 2H), 7.78 (dd, J=8.0, 1.5 Hz, 1H), 7.58-7.52 (m, 2H), 7.51-7.46 (m, 1H), 5.67 (s, 2H), 4.30 (q, J=7.1 Hz, 2H), 3.54-3.50 (m, 2H), 3.29-3.25 (m, 2H), 3.08 (s, 3H), 1.32 (t, J=7.1 Hz, 3H).

Workup

  1. customwas degassed with nitrogen for 10 min in a sealable tube
  2. customthe pressure tube was sealed
  3. temperatureThe reaction mixture was cooled to 23° C.
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. customThe residue was purified by FCC (5-45% EtOAc/hexanes)

Sources & evidence

ORD record
ord-fef5e52cde0f49978cd58c2863104a69
Source dataset
uspto-grants-2015_01
Patent number
US08937078B2

Reaction notes

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