3-Methoxyphenol → ethyl ((1S)-5-{3-[[2-(3-methoxyphenoxy)-5-methyl-4-pyrimidinyl](methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

HRID 603487Notes

Reaction equation

C([O-])([O-])=O.[K+].[K+].[CH3:7][O:8][C:9]1[CH:10]=[C:11]([OH:15])[CH:12]=[CH:13][CH:14]=1.Cl[C:17]1[N:22]=[C:21]([N:23]([CH3:43])[CH2:24][CH2:25][CH2:26][O:27][C:28]2[CH:29]=[C:30]3[C:34](=[CH:35][CH:36]=2)[C@H:33]([CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:32][CH2:31]3)[C:20]([CH3:44])=[CH:19][N:18]=1>CN(C=O)C>[CH3:7][O:8][C:9]1[CH:10]=[C:11]([CH:12]=[CH:13][CH:14]=1)[O:15][C:17]1[N:22]=[C:21]([N:23]([CH3:43])[CH2:24][CH2:25][CH2:26][O:27][C:28]2[CH:29]=[C:30]3[C:34](=[CH:35][CH:36]=2)[C@H:33]([CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:32][CH2:31]3)[C:20]([CH3:44])=[CH:19][N:18]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a suspension of K2CO3 (132 mg, 0.96 mmol) in DMF (5 mL) was added 3-methoxyphenol (36 mg, 0.290 mmol), followed by the portionwise addition of ethyl ((1S)-5-{3-[(2-chloro-5-methyl-4-pyrimidinyl)(methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate prepared in Example 342. The reaction mixture was stirred at 80° C. for 48 h, and then concentrated under reduced pressure. The residue was purified by silica gel flash chromatography to yield the title compound (56.5 mg, 47%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 1.29 (t, 3H), 1.71-1.83 (m, 1H), 2.02 (m, 2H), 2.28 (s, 3H), 2.35-2.47 (m, 2H), 2.75 (dd, 1H), 2.79-2.96 (m, 2H), 3.15 (s, 3H), 3.49-3.57 (m, 1H), 3.56-3.61 (m, 2H), 3.78 (s, 3H), 3.81 (t, 2H), 4.19 (q, 2H), 6.64 (dd, 1H), 6.69-6.78 (m, 3H), 7.05 (d, 1H), 7.21-7.27 (m, 2H), 7.80 (s, 1H); LC-MS: RT=2.85 min, (M+H)+ 506.3.

Workup

concentrationconcentrated under reduced pressure
customThe residue was purified by silica gel flash chromatography

Sources & evidence

ORD record: ord-85e4861de60c4a8a9791f3be36a00e3a
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07906653B2

Reaction notes

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