Trifluoroacetic acid → 2-[4-(4-Cyclobutylmethoxy-benzoyl)-piperidin-1-yl]-acetic acid

HRID 713527Notes

Reaction equation

HRID 713527 reaction equation
[CH2:1]([O:3][C:4]1[CH:21]=[CH:20][C:7]([C:8]([CH:10]2[CH2:15][CH2:14][N:13]([CH2:16][C:17]([OH:19])=O)[CH2:12][CH2:11]2)=[O:9])=[CH:6][CH:5]=1)[CH3:2].F[C:23]1[CH:40]=CC(C(C2CCN(CC(O)=O)CC2)=O)=C[CH:24]=1.C1(CO)CCC1.[CH:47]1([CH2:51][O:52][C:53]2[CH:70]=[CH:69][C:56]([C:57]([CH:59]3[CH2:64][CH2:63][N:62]([CH2:65][C:66]([OH:68])=[O:67])[CH2:61][CH2:60]3)=[O:58])=[CH:55][CH:54]=2)[CH2:50][CH2:49][CH2:48]1.[NH2:71][CH2:72][C:73]1[NH:74][C:75](=[O:83])[C:76]2[CH2:82][O:81][CH2:80][CH2:79][C:77]=2[N:78]=1.C(O)(C(F)(F)F)=O>C(#N)C.O>[CH:47]1([CH2:51][O:52][C:53]2[CH:70]=[CH:69][C:56]([C:57]([CH:59]3[CH2:60][CH2:61][N:62]([CH2:65][C:66]([OH:68])=[O:67])[CH2:63][CH2:64]3)=[O:58])=[CH:55][CH:54]=2)[CH2:50][CH2:49][CH2:48]1.[CH:2]1([CH2:1][O:3][C:4]2[CH:5]=[CH:6][C:7]([C:8]([CH:10]3[CH2:11][CH2:12][N:13]([CH2:16][C:17]([NH:71][CH2:72][C:73]4[NH:74][C:75](=[O:83])[C:76]5[CH2:82][O:81][CH2:80][CH2:79][C:77]=5[N:78]=4)=[O:19])[CH2:14][CH2:15]3)=[O:9])=[CH:20][CH:21]=2)[CH2:40][CH2:23][CH2:24]1

Participants

9

Reactant 6

HCID 6422Trifluoroacetic acidHCID 78130CyclobutylcarbinolHCID 712264022-(4-(4-Fluorobenzoyl)piperidin-1-YL)acetic acidHCID 712272202-[4-(4-Cyclobutylmethoxy-benzoyl)-piperidin-1-yl]-acetic acidHCID 712274202-(4-(4-Ethoxybenzoyl)piperidin-1-yl)acetic acidHCID 1357418942-(Aminomethyl)-7,8-dihydro-3H-pyrano[4,3-D]pyrimidin-4(5H)-one

Product 2

HCID 712272202-[4-(4-Cyclobutylmethoxy-benzoyl)-piperidin-1-yl]-acetic acidHCID 1362373212-[4-(4-Cyclobutylmethoxy-benzoyl)-piperidin-1-yl]-N-(4-oxo-3,5,7,8-tetrahydro-4H-pyrano[4,3-d]pyrimidin-2-ylmethyl)-acetamide

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

2-[4-(4-Cyclobutylmethoxy-benzoyl)-piperidin-1-yl]-acetic acid was prepared following the general procedures for the synthesis of 2-(4-(4-ethoxybenzoyl)piperidin-1-yl)acetic acid from 2-(4-(4-fluorobenzoyl)piperidin-1-yl)acetic acid and cyclobutyl-methanol. The title compound (24.7 mg, 0.047 mmol) was prepared following the general procedure of Example 1 from 2-[4-(4-cyclobutylmethoxy-benzoyl)-piperidin-1-yl]-acetic acid and 2-aminomethyl-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one. MS (ESI) m/z 495.5 (M+H+); HPLC (Insertsil ODS3 100×3 mm C-18 column: mobile phase: 5-95% acetonitrile/water with 0.1% TFA, at 1 mL/min over 7.75 min.) t=1.53 min. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.72 (d, J=2.53 Hz, 2H), 1.77-1.96 (m, 5H), 2.03-2.13 (m, 2H), 2.19-2.32 (m, 2H), 2.50 (br. s., 3H), 2.66-2.82 (m, 1H), 2.90-3.03 (m, 3H), 3.24-3.40 (m, 2H), 3.82 (t, J=5.56 Hz, 2H), 4.04 (d, J=6.57 Hz, 2H), 4.19 (d, J=5.56 Hz, 2H), 4.34 (s, 2H), 7.03 (d, J=9.09 Hz, 2H), 7.94 (d, J=8.59 Hz, 2H), 8.21 (t, J=5.81 Hz, 1H), 12.37 (br. s., 1H). HRMS calculated for C27H35N4O5: 495.2607 (M+H). found (ESI, [M+H]+): 495.2627.

Sources & evidence

ORD record
ord-eed11dfcd7ae4b0f8cf67e640b595ca2
Source dataset
uspto-grants-2015_11
Patent number
US09181266B2

Reaction notes

Loading…