Methanol → HCID 178466845, compound

HRID 511506Notes

Reaction equation

HRID 511506 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[CH:25]=[CH:26][C:27]([C@H:35]4[CH2:40][CH2:39][C@H:38]([C:41]([O:43]CC)=[O:42])[CH2:37][CH2:36]4)=[C:28]4[C:32]=3[C:31](=[O:33])[N:30]([CH3:34])[CH2:29]4)[C:20]([C:46]([F:49])([F:48])[F:47])=[CH:19][N:18]=2)=[C:12]([O:50][CH2:51][CH3:52])[CH:11]=1)([O:6][CH2:7][CH3:8])=[O:5])[CH3:2].C1COCC1.CO.O.[OH-].[Li+].O>>[CH2:7]([O:6][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[CH:25]=[CH:26][C:27]([C@H:35]4[CH2:40][CH2:39][C@H:38]([C:41]([OH:43])=[O:42])[CH2:37][CH2:36]4)=[C:28]4[C:32]=3[C:31](=[O:33])[N:30]([CH3:34])[CH2:29]4)[C:20]([C:46]([F:47])([F:49])[F:48])=[CH:19][N:18]=2)=[C:12]([O:50][CH2:51][CH3:52])[CH:11]=1)([O:3][CH2:1][CH3:2])=[O:5])[CH3:8]

Participants

6

Reactant 5

HCID 887MethanolHCID 962WaterHCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 178466847HCID 178466847, compound

Product 1

HCID 178466845HCID 178466845, compoundYield 100%

Procedure

Ethyl trans-4-(7-{[2-({4-[(diethoxyphosphoryl)methyl]-2-ethoxyphenyl}amino)-5-(trifluoromethyl)pyrimidin-4-yl]amino}-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl)cyclohexanecarboxylate (Example 245, 23.4 mg, 0.031 mmol) was taken up in THF (0.042 mL, 0.52 mmol) and MeOH (0.042 mL, 1.0 mmol). This was treated with a solution of lithium hydroxide, monohydrate (6.57 mg, 0.16 mmol) in H2O (0.042 mL, 2.30 mmol) and allowed to stir at rt for 30 hrs. The reaction was concentrated in vacuo to a solid and was purified by CombiFlash®Rf 4X Organic Purification System [24 g RediSep® Normal-phase GOLD Silica Flash Column, dried loaded, elution gradient: 0>5% MeOH in DCM] to afford 22.3 mg (99%) of the desired product. 1H NMR (400 MHz, MeOD) δ ppm 4.54 (s, 1 H), 4.05-4.21 (m, 6 H), 3.29 (s, 2 H), 3.20 (s, 3 H), 2.60-2.69 (m, 1 H), 2.38-2.48 (m, 1 H), 2.15 (d, J=11.87 Hz, 2H), 1.91-1.98 (m, 2 H), 1.56-1.77 (m, 4 H), 1.43 (t, J=6.95 Hz, 3 H), 1.30 (t, 6 H). MS (ES+): m/z 720.22/721.25 (100/98) [MH+]. HPLC: tR=1.54 min (Micromass TOF: polar—3 min).

Workup

  1. concentrationThe reaction was concentrated in vacuo to a solid
  2. customwas purified by CombiFlash®Rf 4X Organic Purification System [24 g RediSep® Normal-phase GOLD Silica Flash Column, dried loaded, elution gradient: 0>5% MeOH in DCM]

Sources & evidence

ORD record
ord-3ccd724585fe4b8db45f627eb55d74b4
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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