Diisopropylethylamine → 5-Bromo-6-(3-methyl-oxetan-3-ylmethoxy)-pyridine-2-carboxylic acid (1-methyl-1-thiazol-2-yl-ethyl)-amide

HRID 927723Notes

Reaction equation

HRID 927723 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:15]([OH:17])=O)=[N:6][C:7]=1[O:8][CH2:9][C:10]1([CH3:14])[CH2:13][O:12][CH2:11]1.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.CCN(C(C)C)C(C)C.[CH3:45][C:46]([CH3:53])([C:48]1[S:49][CH:50]=[CH:51][N:52]=1)[NH2:47]>CN(C=O)C>[CH3:45][C:46]([NH:47][C:15]([C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[C:7]([O:8][CH2:9][C:10]2([CH3:14])[CH2:11][O:12][CH2:13]2)[N:6]=1)=[O:17])([C:48]1[S:49][CH:50]=[CH:51][N:52]=1)[CH3:53]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 282862032-(1,3-Thiazol-2-yl)propan-2-amineHCID 710878905-Bromo-6-(3-methyl-oxetan-3-ylmethoxy)-pyridine-2-carboxylic acid

Product 1

HCID 710935485-Bromo-6-(3-methyl-oxetan-3-ylmethoxy)-pyridine-2-carboxylic acid (1-methyl-1-thiazol-2-yl-ethyl)-amideYield 23%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-bromo-6-(3-methyl-oxetan-3-ylmethoxy)-pyridine-2-carboxylic acid (Example 280b) (30 mg, 100 μmol) in dry DMF (1 ml) was added 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (29.1 mg, 105 μmol) and Hunig's base (52.4 uL, 300 umol). The reaction was stirred at r.t for 30 min, followed by addition of α,α-Dimethyl-2-thiazolemethanamine (Example 12c) (14.2 mg, 100 μmol). The reactions was stirred at room temperature overnight and monitored by LC-MS. When the reaction was complete, purification was directly done by preparative HPLC without any work-up procedure to give the title compound (9.8 mg, 23%). MS (EI): m/e=425.9 [M+H]+.

Workup

  1. stirringThe reactions was stirred at room temperature overnight
  2. custompurification

Sources & evidence

ORD record
ord-9bcc9112f1f04b9fb575bf1aa8cef16c
Source dataset
uspto-grants-2016_03
Patent number
US09290451B2

Reaction notes

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