6-Bromo-3-fluoropyridine-2-carboxylic acid → cis (+/-)-Tert-butyl 1-(3-(6-bromo-3-fluoropicolinamido)pyridin-4-yl)-5-(hydroxymethyl)piperidin-3-ylcarbamate

HRID 69989Notes

Reaction equation

HRID 69989 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][C@H:12]([CH2:14][O:15][Si](C(C)(C)C)(C)C)[CH2:11][C@H:10]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:9]1.[Br:31][C:32]1[N:37]=[C:36]([C:38]([OH:40])=O)[C:35]([F:41])=[CH:34][CH:33]=1>>[Br:31][C:32]1[N:37]=[C:36]([C:38]([NH:1][C:2]2[CH:3]=[N:4][CH:5]=[CH:6][C:7]=2[N:8]2[CH2:13][C@H:12]([CH2:14][OH:15])[CH2:11][C@H:10]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:28])([CH3:27])[CH3:29])[CH2:9]2)=[O:40])[C:35]([F:41])=[CH:34][CH:33]=1

Participants

3

Reactant 2

HCID 707008736-Bromo-3-fluoropyridine-2-carboxylic acidHCID 131731822cis (+/-)-Tert-butyl 1-(3-aminopyridin-4-yl)-5-((tert-butyldimethylsilyloxy)methyl)piperidin-3-ylcarbamate

Product 1

HCID 131731823cis (+/-)-Tert-butyl 1-(3-(6-bromo-3-fluoropicolinamido)pyridin-4-yl)-5-(hydroxymethyl)piperidin-3-ylcarbamate

Procedure

Following Method 11 of Example 305, cis (+/−)-tert-butyl 1-(3-aminopyridin-4-yl)-5-((tert-butyldimethylsilyloxy)methyl)piperidin-3-ylcarbamate and 6-bromo-3-fluoropicolinic acid were coupled. Following purification by RP HPLC the product fractions were allowed to stand at it overnight in the 0.1% TFA acetonitile/water solution which removed the silyl group. Upon subsequent lyophilization, cis (+/−)-tert-butyl 1-(3-(6-bromo-3-fluoropicolinamido)pyridin-4-yl)-5-(hydroxymethyl)piperidin-3-ylcarbamate was obtained and used in Suzuki reactions directly. LCMS (m/z): 524.0/526.0 (MH+); LC Rt=2.90 min.

Workup

  1. custompurification by RP HPLC the product fractions
  2. customto stand at it overnight in the 0.1% TFA acetonitile/water solution which
  3. customremoved the silyl group

Sources & evidence

ORD record
ord-9106101073804df29c0584bf25063ad5
Source dataset
uspto-grants-2014_09
Patent number
US08822497B2

Reaction notes

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