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Sodium Iodide → Sodium ethyl (4-{[4-({7-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate

HRID 1947984
Notes
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Reaction equation

HRID 1947984 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][N:5]1[CH:9]=[C:8]([C:10]2[CH:11]=[CH:12][C:13]([NH:21][C:22]3[C:27]([C:28]([F:31])([F:30])[F:29])=[CH:26][N:25]=[C:24]([NH:32][C:33]4[CH:47]=[CH:46][C:36]([CH2:37][P:38](=[O:45])([O:42]CC)[O:39][CH2:40][CH3:41])=[CH:35][CH:34]=4)[N:23]=3)=[C:14]3[C:18]=2[CH2:17][N:16]([CH3:19])[C:15]3=[O:20])[CH:7]=[N:6]1.[Na+:48].[I-]>CCC(C)=O>[CH2:40]([O:39][P:38]([CH2:37][C:36]1[CH:46]=[CH:47][C:33]([NH:32][C:24]2[N:23]=[C:22]([NH:21][C:13]3[CH:12]=[CH:11][C:10]([C:8]4[CH:7]=[N:6][N:5]([CH2:4][CH2:3][CH2:2][OH:1])[CH:9]=4)=[C:18]4[C:14]=3[C:15](=[O:20])[N:16]([CH3:19])[CH2:17]4)[C:27]([C:28]([F:30])([F:31])[F:29])=[CH:26][N:25]=2)=[CH:34][CH:35]=1)(=[O:42])[O-:45])[CH3:41].[Na+:48]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 5238Sodium IodideHCID 58292962Diethyl (4-{[4-({7-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate

Product 1

HCID 86697677Sodium ethyl (4-{[4-({7-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate

Reagents, catalysts & solvents 1

HCID 6569
Methyl Ethyl Ketone
Solvent

Procedure

A mixture of Example 156 (172 mg, 0.255 mmol) in MEK (6 mL) was treated with of NaI (165 mg, 1.102 mmol) and irradiated on the microwave at 120° C. for 6 hours. The cooled reaction mixture was filtered, the solids were washed with ice cold acetone and dried in vacuo to afford the title compound as alight brown solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.64 (br s, 1H), 9.72 (s, 1H), 9.19 (br s, 1H), 8.47 (br s, 1H), 8.40 (s, 1H), 8.19 (br s, 1H), 7.75 (br s, 1H), 7.28 (br s, 4H), 6.34 (br s, 1H), 4.63 (s, 2H), 4.20 (t, J=6.2 Hz, 2H), 3.60 (quin, J=7.1 Hz, 2H), 3.42-3.51 (m, 2H), 3.11 (s, 3H), 2.73 (d, J=19.5 Hz, 2H), 1.94 (quin, J=6.1 Hz, 2H), 0.94 (t, J=6.9 Hz, 3H). MS (ES+): m/z 646.20 (100) [MH+]; HPLC: tR=1.12 min (UPLC TOF, polar—3 min).

Workup

  1. customirradiated on the microwave at 120° C. for 6 hours
  2. customThe cooled reaction mixture
  3. filtrationwas filtered
  4. washthe solids were washed with ice cold acetone
  5. customdried in vacuo

Sources & evidence

ORD record
ord-b7cbba3fc0cf4b1fbe34900f80529918
Source dataset
uspto-grants-2013_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08399433B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes