2-(Di-tert-butylphosphino)biphenyl → HCID 59856805, compound

HRID 1174760Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][CH2:12][CH2:13][O:14][CH:15]([CH3:17])[CH3:16])(=[O:10])=[O:9])=[CH:4][C:3]=1[F:18].[CH:19]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28]([O:31][C:32]2[C:37]([CH3:38])=[C:36](Cl)[N:35]=[CH:34][N:33]=2)[CH2:27][CH2:26]1)=[O:24])([CH3:21])[CH3:20].C1(C2C=CC=CC=2)C=CC=CC=1P(C(C)(C)C)C(C)(C)C.CC(C)([O-])C.[Na+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:19]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28]([O:31][C:32]2[C:37]([CH3:38])=[C:36]([NH:1][C:2]3[CH:7]=[CH:6][C:5]([S:8](=[O:10])(=[O:9])[NH:11][CH2:12][CH2:13][O:14][CH:15]([CH3:16])[CH3:17])=[CH:4][C:3]=3[F:18])[N:35]=[CH:34][N:33]=2)[CH2:27][CH2:26]1)=[O:24])([CH3:21])[CH3:20]

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 4-amino-3-fluoro-N-(2-isopropoxy-ethyl)-benzenesulfonamide (116 mg, 0.42 mmol), 4-(6-chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester (100 mg, 0.3 mmol), palladium acetate (3 mg, 0.017 mmol), biphenyl-2-yl-di-tert-butyl-phosphane (7.1 mg, 0.034 mmol), and sodium t-butoxide (87 mg, 0.90 mmol) in dioxane (2 mL) was heated under microwave irradiation for 60 min at 150° C. The crude mixture was concentrated in vacuo and purified by HPLC to provide Compound A106 as a brown solid (50 mg, 22%). 1H NMR (CDCl3, 400 MHz) δ 1.04 (d, 6H), 1.19 (d, 6H), 1.67-1.78 (m, 2H), 1.89-1.99 (m, 5H), 3.05 (t, 2H), 3.30-3.40 (m, 4H), 3.42-3.52 (m, 1H), 3.66-3.76 (m, 1H), 4.87 (h, 1H), 5.19-5.38 (m, 2H), 7.58 (t, 3H), 7.90-7.98 (s broad, 1H), 8.24 (t, 1H), 8.35 (s, 1H). Exact mass calculated for C23H36FN5O6S 553.65, found 554.6 (MH+).

Workup

concentrationThe crude mixture was concentrated in vacuo
custompurified by HPLC

Sources & evidence

ORD record: ord-bbf3d56f14fc458da6ed91fe233146c8
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07838525B2

Reaction notes

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