Sodium Iodide → Ethyl hydrogen (4-{[4-{[6-bromo-2-(methylcarbamoyl)pyridin-3-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

HRID 2279823Notes

Reaction equation

[CH2:1]([O:3][P:4]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[N:22]=[C:21]([NH:23][C:24]3[C:25]([C:31](=[O:34])[NH:32][CH3:33])=[N:26][C:27]([Br:30])=[CH:28][CH:29]=3)[C:20]([C:35]([F:38])([F:37])[F:36])=[CH:19][N:18]=2)=[C:12]([O:39][CH3:40])[CH:11]=1)(=[O:8])[O:5]CC)[CH3:2].[I-].[Na+]>N1C=CC=CC=1>[Br:30][C:27]1[N:26]=[C:25]([C:31](=[O:34])[NH:32][CH3:33])[C:24]([NH:23][C:21]2[C:20]([C:35]([F:38])([F:36])[F:37])=[CH:19][N:18]=[C:17]([NH:16][C:13]3[CH:14]=[CH:15][C:10]([CH2:9][P:4](=[O:5])([OH:8])[O:3][CH2:1][CH3:2])=[CH:11][C:12]=3[O:39][CH3:40])[N:22]=2)=[CH:29][CH:28]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A solution of {4-[4-(6-bromo-2-methylcarbamoyl-pyridin-3-ylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-3-methoxy-benzyl}-phosphonic acid diethyl ester (Compound 38D, 610 mg, 0.94 mmol) in pyridine (9.57 mL) was treated with Sodium iodide (847 mg, 5.65 mmol) and heated at 120° C. for 16 hrs overnight. The reaction solution was concentrated in vacuo and purified using a Teledyne ISCO Combiflash® Rf system [5%→95% MeOH in Water over 25 CV] to afford 543 mg of the title compound (93%). 1H NMR (400 MHz, CD3OD) 8.99 (br. s, 1H), 8.80 (d, J=4.6 Hz, 1H), 8.34 (s, 1H), 7.55 (d, J=9.1 Hz, 1H), 7.10 (s, 1H), 6.90 (d, J=8.1 Hz, 1H), 3.83-3.95 (m, 5H), 3.04 (s, 1H), 2.99 (s, 1H), 2.93 (d, J=5.1 Hz, 3H), 1.21 (t, J=7.0 Hz, 3H). MS (ESI): m/z 619.42/621.44 [M+H]+. UPLC: tR=1.24 min (UPLC-TOF: polar—2 min).

Workup

concentrationThe reaction solution was concentrated in vacuo
custompurified

Sources & evidence

ORD record: ord-cad5524aa20b427684e59eea2cf00b58
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133224B2

Reaction notes

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