(3S,4S)-4-(Hydroxymethyl)pyrrolidin-3-ol Hydrochloride → 5-Bromo-6-((3R,4R)-3-hydroxy-4-(hydroxymethyl)pyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 525664Notes

Reaction equation

HRID 525664 reaction equation
[Br:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].Cl.[OH:24][CH2:25][C@@H:26]1[CH2:30][NH:29][CH2:28][C@H:27]1[OH:31]>>[Br:1][C:2]1[C:3]([N:29]2[CH2:30][C@H:26]([CH2:25][OH:24])[C@@H:27]([OH:31])[CH2:28]2)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8]

Participants

3

Reactant 2

HCID 69805812(3S,4S)-4-(Hydroxymethyl)pyrrolidin-3-ol HydrochlorideHCID 867025955-bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 899072625-Bromo-6-((3R,4R)-3-hydroxy-4-(hydroxymethyl)pyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Procedure

The title compound was prepared in an analogous fashion to that described in Stage 6.1 using 5-bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 6.2) and trans-4-(hydroxymethyl)pyrrolidin-3-ol hydrochloride to afford an off-white solid. UPLC-MS (Condition 3) tR=0.98 min, m/z=476.2/478.2 [M+H]+, m/z=474.0/476.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.11-2.23 (m, 1H) 3.25-3.34 (m, 2H) 3.39-3.49 (m, 1H) 3.50-3.62 (m, 2H) 3.83-3.96 (m, 2H) 4.04-4.12 (m, 1H) 4.70 (t, J=5.27 Hz, 1H) 5.07 (d, J=4.37 Hz, 1H) 7.33 (d, J=8.75 Hz, 2H) 7.83 (d, J=9.00 Hz, 2H) 8.32 (d, J=2.06 Hz, 1H) 8.66 (d, J=1.80 Hz, 1H) 10.21 (s, 1H).

Workup

  1. customto afford an off-white solid

Sources & evidence

ORD record
ord-3937d04d9e034fc78d72fb5cffa52b8c
Source dataset
uspto-grants-2016_05
Patent number
US09340537B2

Reaction notes

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