Phosphorodichloridic acid, phenyl ester → 2-Chloro-5-[2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-nicotinonitrile

HRID 55866

Reaction equation

CO[C:3]1[N:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]3[CH:19]=[N:20][C:21]([CH2:24][N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[CH:22][CH:23]=3)[N:12]=2)=[CH:7][C:4]=1[C:5]#[N:6].C1(OP(Cl)([Cl:40])=O)C=CC=CC=1>O>[Cl:40][C:3]1[N:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]3[CH:19]=[N:20][C:21]([CH2:24][N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[CH:22][CH:23]=3)[N:12]=2)=[CH:7][C:4]=1[C:5]#[N:6]

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of compound 17 (1.5 g, 3.7 mmol) and phenylphosphoro dichloridate (5 mL) was heated at 130° C. for 5 h. The reaction mixture was cooled to rt, diluted with cold water (10 mL), cooled to 0° C., quenched with saturated NaHCO3 solution and extracted with EtOAc (2×50 mL). The combined organic layer was washed with brine (50 mL), dried (Na2SO4) and evaporated. The crude compound was purified by trituration with EtOAc to obtain 18 (0.7 g, 46%) as a pale brown solid. Rf: 0.5 (10% MeOH/DCM); (m/z): 408 [M+1]+; 1H NMR (400 MHz, DMSO-d6): δ10.01 (1H, s), 9.40 (1H, d, J=2.4 Hz), 9.11 (1H, d, J=2.4 Hz), 8.85 (1H, d, J=2.4 Hz), 8.70 (1H, d, J=5.2 Hz), 8.21-8.18 (1H, dd, J=2.4, 8.8 Hz), 7.62 (1H, d, J=5.6 Hz), 7.40 (1H, d, J=8.4 Hz), 3.59-3.54 (6H, m), 2.46-2.41 (4H, m).

Workup

temperatureThe reaction mixture was cooled to rt
temperaturecooled to 0° C.
customquenched with saturated NaHCO3 solution
extractionextracted with EtOAc (2×50 mL)
washThe combined organic layer was washed with brine (50 mL)
dry with materialdried (Na2SO4)
customevaporated
customThe crude compound was purified by trituration with EtOAc

Sources & evidence

ORD record: ord-8d56d8e09b2c4cef9b7f7c159e5a609d
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09433622B2

Linked notes

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