Tetrahydrofuran → HCID 68487879, compound

HRID 1428828Notes

Reaction equation

HRID 1428828 reaction equation
C(=O)([O-])[O-].[K+].[K+].[CH3:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1B(O)O.[CH2:17]([O:19][C:20]([C:22]1[CH:23]=[N:24][N:25]([C:27]2[N:36]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[C:35](=[O:45])[C:34]3[C:29](=[CH:30][CH:31]=[C:32](I)[CH:33]=3)[N:28]=2)[CH:26]=1)=[O:21])[CH3:18].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>[CH2:17]([O:19][C:20]([C:22]1[CH:23]=[N:24][N:25]([C:27]2[N:36]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[C:35](=[O:45])[C:34]3[C:29](=[CH:30][CH:31]=[C:32]([C:9]4[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=4[CH3:7])[CH:33]=3)[N:28]=2)[CH:26]=1)=[O:21])[CH3:18]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 27332672-Methylphenyl boronic acidHCID 68487682HCID 68487682, compound

Product 1

HCID 68487879HCID 68487879, compoundYield 90%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
80 °C

Procedure

A mixture of potassium carbonate (85.4 mg 0.618 mmol), 2-methylphenylboronic acid (63.3 mg, 0.466 mmol), 1-[6-iodo-4-oxo-3-(2-trimethylsilanyl-ethoxymethyl)-3,4-dihydro-quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (110 mg, 0.204 mmol), and THF (1.5 ml) was degassed for 5 minutes with nitrogen in a sealable tube. The dichloromethane adduct of 1,1′-bis(diphenylphosphino)ferrocene]dichloro palladium (20.2 mg, 0.0246 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 (10 ml), and filtered. The filtrate was concentrated. The residue was purified by FCC (3-40% EtOAc/hexanes) to yield the titled compound (92.0 mg, 90%). MS (ESI): mass calcd. for C27H32N4O4Si, 504.22; m/z found, 446.6 [M−CH2OCH2CH2+H]+. 1H NMR (600 MHz, CDCl3): 8.68 (d, J=0.6 Hz, 1H), 8.31-8.30 (m, 1H), 8.18 (d, J=0.6 Hz, 1H), 7.79 (dd, J=8.3, 2.1 Hz, 1H), 7.76-7.74 (m, 1H), 7.33-7.28 (m, 4H), 5.91 (s, 2H), 4.39-4.35 (m, 2H), 4.37 (q, J=7.2 Hz, 2H), 2.31 (s, 3H), 1.39 (t, J=7.1 Hz, 3H), 0.83-0.79 (m, 2H), −0.08 (s, 9H).

Workup

  1. customwas degassed for 5 minutes with nitrogen 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 (3-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-58215e58428b4935a76edc4151dbcc9c
Source dataset
uspto-grants-2015_01
Patent number
US08937078B2

Reaction notes

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