1-(Bromomethyl)-2-phenylbenzene → HCID 66932490, compound
Reaction equation
[CH3:1][O:2][C:3](=[O:29])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:25](=[CH:26][CH:27]=1)[O:24][C:11]1([CH2:16][CH2:15][N:14]([C:17](OC(C)(C)C)=O)[CH2:13][CH2:12]1)[CH2:10][C:9]2=[O:28].[C:30]1([C:36]2[CH:43]=[CH:42][CH:41]=[CH:40][C:37]=2CBr)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>>[CH3:1][O:2][C:3](=[O:29])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:25](=[CH:26][CH:27]=1)[O:24][C:11]1([CH2:12][CH2:13][N:14]([CH2:17][C:43]3[CH:42]=[CH:41][CH:40]=[CH:37][C:36]=3[C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH2:15][CH2:16]1)[CH2:10][C:9]2=[O:28]Participants
Procedure
(E)-3-{4-Oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (169 mg, 0.500 mmol, Intermediate 1, hydrochloride salt) was alkylated using 2-phenylbenzyl bromide (0.18 ml, 1.0 mmol) following the procedure described in Example 2, Step A, giving (E)-3-{1′-(biphenyl-2-yl-methyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (163 mg) as a white solid. The intermediate was hydrolyzed as described in Example 55, Step B, giving (E)-3-{1′-(Biphenyl-2-yl-methyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid (162 mg) as a white solid (hydrochloride salt). The acid was suspended in DCM (5 ml), TEA (0.07 ml, 0.47 mmol) was added, and the clear solution was treated with NH2OTHP following the procedure described in Example 1, Step B, giving (E)-3-{1′-(biphenyl-2-yl-methyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide (163 mg) as a light yellow solid. The compound was dissolved in DCM (5 ml) and treated with 4 M HCl in dioxane (0.4 ml, 1.6 mmol) as described in Example 55, Step D, giving a light yellow solid (114 mg, hydrochloride salt).
Sources & evidence
- ORD record
- ord-a29b1b167d1b4876b12b4930880ade1f
- Source dataset
- uspto-grants-2013_11
- Patent number
- US08592444B2
Reaction notes
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