Sodium Carbonate → (R)-cyclohexyl(4-(4-(4-(hydroxymethyl)phenyl)phthalazin-1-yl)-3-methylpiperazin-1-yl)methanone

HRID 1689978Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([N:12]2[CH2:17][CH2:16][N:15]([C:18]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)=[O:19])[CH2:14][C@H:13]2[CH3:26])=[N:4][N:3]=1.[OH:27][CH2:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:20]1([C:18]([N:15]2[CH2:16][CH2:17][N:12]([C:5]3[C:6]4[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:2]([C:32]4[CH:33]=[CH:34][C:29]([CH2:28][OH:27])=[CH:30][CH:31]=4)=[N:3][N:4]=3)[C@H:13]([CH3:26])[CH2:14]2)=[O:19])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

Conditions

Temperature: 100 °C

Procedure

(R)-(4-(4-chlorophthalazin-1-yl)-3-methylpiperazin-1-yl)(cyclohexyl)methanone (JK-21) (150 mg, 0.402 mmol), 4-(hydroxymethyl)phenylboronic acid (85.6 mg, 0.563 mmol), and tetrakis(triphenylphosphine)palladium (0) (23.6 mg, 0.0201 mmol) were dissolved in toluene (5 mL) and aqueous sodium carbonate (2.0M, 0.500 mL) under an atmosphere of argon. The reaction was heated at 100° C. for 23 hours, then cooled and taken up in ethyl acetate (80 mL). After washing with aqueous K2CO3 (10%), water, and saturated sodium chloride, the organics were dried (MgSO4) and evaporated to give a yellow oil. Chromatography over silica gel with a gradient of hexanes/0-100% ethyl acetate gave a pale yellow solid, JK-29. MS (M+H)+=445.4.

Workup

temperaturecooled
washAfter washing with aqueous K2CO3 (10%), water, and saturated sodium chloride
dry with materialthe organics were dried (MgSO4)
customevaporated
customto give a yellow oil

Sources & evidence

ORD record: ord-092b73b9d77a4221ae5cc37f8eeb1d85
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08153633B2

Reaction notes

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