Methanol → HCID 178466844, compound

HRID 511505Notes

Reaction equation

HRID 511505 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 178466846HCID 178466846, compound

Product 1

HCID 178466844HCID 178466844, compoundYield 99.3%

Procedure

Ethyl cis-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 244, 72.0 mg, 0.096 mmol) was taken up in THF (0.13 mL, 1.60 mmol) and MeOH (0.13 mL, 3.20 mmol). This was treated with a solution of lithium hydroxide, monohydrate (20.2 mg, 0.48 mmol) in H2O (0.13 mL, 7.2 mmol) and was 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 68.6 mg (99%) of the desired product. 1H NMR (400 MHz, MeOD) δ ppm 8.43 (d, J=9.09 Hz, 1 H), 8.34 (s, 1H), 7.88 (d, J=8.34 Hz, 1 H), 7.26 (d, J=8.84 Hz, 1 H), 7.03 (t, J=2.02 Hz, 1 H), 6.90 (dt, J=8.21, 2.21 Hz, 1 H), 4.51 (s, 2 H), 4.03-4.17 (m, 6 H), 3.27 (s, 2 H), 3.18 (s, 3 H), 2.74 (br. s., 1 H), 2.61-2.70 (m, 1 H), 2.30 (d, J=12.38 Hz, 2 H), 1.66-1.82 (m, 6 H), 1.41 (t, J=6.95 Hz, 3 H), 1.28 (t, J=7.07 Hz, 6 H). MS (ES+): m/z 720.22/721.26 (100/98) [MH+]. HPLC: tR=1.62 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-20eae04ad75c4eb5aa3eec930bb47cd1
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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