(3S,4S)-4-(Hydroxymethyl)pyrrolidin-3-ol Hydrochloride → 4-(trans-3-Hydroxy-4-(hydroxymethyl)pyrrolidin-1-yl)-3-(thiazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide

HRID 525645Notes

Reaction equation

HRID 525645 reaction equation
F[C:2]1[CH:21]=[CH:20][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][CH:10]=2)=[O:7])=[CH:4][C:3]=1[C:22]1[S:26][CH:25]=[N:24][CH:23]=1.Cl.[OH:28][CH2:29][C@@H:30]1[CH2:34][NH:33][CH2:32][C@H:31]1[OH:35]>>[OH:35][C@H:31]1[C@H:30]([CH2:29][OH:28])[CH2:34][N:33]([C:2]2[CH:21]=[CH:20][C:5]([C:6]([NH:8][C:9]3[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][CH:10]=3)=[O:7])=[CH:4][C:3]=2[C:22]2[S:26][CH:25]=[N:24][CH:23]=2)[CH2:32]1

Participants

3

Reactant 2

HCID 69805812(3S,4S)-4-(Hydroxymethyl)pyrrolidin-3-ol HydrochlorideHCID 899067714-fluoro-3-(thiazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide

Product 1

HCID 1180450464-(trans-3-Hydroxy-4-(hydroxymethyl)pyrrolidin-1-yl)-3-(thiazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide

Procedure

The title compound was prepared in an analogous fashion to that described in Example 4 using 4-fluoro-3-(thiazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide (Stage 1.1) and trans-4-(hydroxymethyl)pyrrolidin-3-ol hydrochloride to afford an off-white solid. UPLC-MS (Condition 3) tR=0.95 min, m/z=480.1 [M+H]+, m/z=478.2 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.04-2.18 (m, 1H) 2.78 (dd, J=10.39, 3.79 Hz, 1H) 2.97 (dd, J=9.90, 5.01 Hz, 1H) 3.18 (dd, J=10.51, 5.62 Hz, 1H) 3.23-3.28 (m, 1H) 3.32-3.37 (m, 1H) 3.37-3.47 (m, 1H) 3.91-4.03 (m, 1H) 4.63 (t, J=5.14 Hz, 1H) 4.94 (d, J=4.16 Hz, 1H) 6.99 (d, J=8.80 Hz, 1H) 7.34 (d, J=8.56 Hz, 2H) 7.83-7.98 (m, 5H) 9.16 (d, J=0.73 Hz, 1H) 10.15 (s, 1H).

Workup

  1. customto afford an off-white solid

Sources & evidence

ORD record
ord-325ed4f7050949df94e5848b00f843eb
Source dataset
uspto-grants-2016_05
Patent number
US09340537B2

Reaction notes

Loading…