Sodium Iodide → Ethyl hydrogen (4-{[4-({2-(diethylcarbamoyl)-4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

HRID 2279709Notes

Reaction equation

HRID 2279709 reaction equation
[CH2:1]([N:3]([CH2:50][CH3:51])[C:4]([C:6]1[CH:11]=[C:10]([C:12]2[CH:13]=[N:14][N:15]([CH2:17][CH2:18][CH2:19][OH:20])[CH:16]=2)[CH:9]=[CH:8][C:7]=1[NH:21][C:22]1[C:27]([C:28]([F:31])([F:30])[F:29])=[CH:26][N:25]=[C:24]([NH:32][C:33]2[CH:47]=[CH:46][C:36]([CH2:37][P:38](=[O:45])([O:42]CC)[O:39][CH2:40][CH3:41])=[CH:35][C:34]=2[O:48][CH3:49])[N:23]=1)=[O:5])[CH3:2].[I-].[Na+]>N1C=CC=CC=1>[CH2:50]([N:3]([CH2:1][CH3:2])[C:4]([C:6]1[CH:11]=[C:10]([C:12]2[CH:13]=[N:14][N:15]([CH2:17][CH2:18][CH2:19][OH:20])[CH:16]=2)[CH:9]=[CH:8][C:7]=1[NH:21][C:22]1[C:27]([C:28]([F:29])([F:30])[F:31])=[CH:26][N:25]=[C:24]([NH:32][C:33]2[CH:47]=[CH:46][C:36]([CH2:37][P:38](=[O:42])([OH:45])[O:39][CH2:40][CH3:41])=[CH:35][C:34]=2[O:48][CH3:49])[N:23]=1)=[O:5])[CH3:51]

Participants

4

Reactant 2

HCID 5238Sodium IodideHCID 86697679diethyl (4-{[4-({2-(diethylcarbamoyl)-4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate2×

Product 1

HCID 86697678Ethyl hydrogen (4-{[4-({2-(diethylcarbamoyl)-4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateYield 76.1%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A mixture of diethyl (4-{[4-({2-(diethylcarbamoyl)-4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (Compound 3B, 228 mg, 311 μmol), sodium iodide (158 mg, 1.06 mmol) in pyridine (3.52 ml) was stirred at reflux for 16 hrs then concentrated in vacuo to a solid which was purified by a Teledyne ISCO Combiflash® Rf system [elution gradient: 5%→95% MeOH in water over 25 CV using a C-18 RP column] to yield the desired product (167 mg, 76%). 1H NMR (400 MHz, CD3OD) δ 8.25 (s, 1H), 8.18 (s, 1H), 7.93 (s, 1H), 7.74 (d, J=1.01 Hz, 2H), 7.69 (d, J=7.07 Hz, 1H), 7.55 (s, 1H), 6.99 (br. s., 1H), 6.52 (br. s., 1H), 4.32 (t, J=6.69 Hz, 2H), 3.88 (s, 3H), 3.71-3.80 (m, 2H), 3.59 (t, J=6.06 Hz, 2H), 3.47 (d, J=6.32 Hz, 2H), 3.14-3.23 (m, 2H), 2.85 (d, J=19.96 Hz, 2H), 2.07-2.16 (m, 2H), 1.11 (t, J=6.82 Hz, 6H), 0.90 (br. s., 3H). MS (ESI): m/z 706.80 [M+H]+. UPLC: tR=1.07 min (UPLC-SQD: analytical—2 min).

Workup

  1. temperatureat reflux for 16 hrs
  2. concentrationthen concentrated in vacuo to a solid which
  3. customwas purified by a Teledyne ISCO Combiflash® Rf system [
  4. washelution gradient

Sources & evidence

ORD record
ord-957a0fbf89a0461c9d91be4f185dfee0
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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