4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride → HCID 59200031, compound

HRID 2382054Notes

Reaction equation

HRID 2382054 reaction equation
[CH3:1][C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][N:5]=[C:4]([C:11]2[S:12][CH:13]=[CH:14][N:15]=2)[N:3]=1.[NH2:16][N:17]1[C:25]2[C:20](=[CH:21][C:22]([F:26])=[CH:23][CH:24]=2)[C:19]([CH2:27][CH2:28][C:29]([CH3:32])([OH:31])[CH3:30])=[CH:18]1.C[N+]1(C2N=C(OC)N=C(OC)N=2)CCOCC1.[Cl-]>CN(C=O)C.C([O-])([O-])=O.[Na+].[Na+]>[F:26][C:22]1[CH:21]=[C:20]2[C:25](=[CH:24][CH:23]=1)[N:17]([NH:16][C:8]([C:7]1[C:2]([CH3:1])=[N:3][C:4]([C:11]3[S:12][CH:13]=[CH:14][N:15]=3)=[N:5][CH:6]=1)=[O:10])[CH:18]=[C:19]2[CH2:27][CH2:28][C:29]([OH:31])([CH3:30])[CH3:32]

Participants

6

Reactant 3

HCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 685521584-(1-amino-5-fluoro-1H-indol-3-yl)-2-methyl-butan-2-olHCID 685536304-methyl-2-(2-thiazolyl)-5-Pyrimidinecarboxylic acid

Product 1

HCID 59200031HCID 59200031, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 4-methyl-2-thiazol-2-yl-pyrimidine-5-carboxylic acid (300 mg, 1.36 mmol) and 4-(1-amino-5-fluoro-1H-indol-3-yl)-2-methyl-butan-2-ol (325 mg, 1.38 mmol) in DMF (5 mL) is stirred at 50° C. for 1 h. The mixture is treated with DMTMM (380 mg, 1.38 mmol) and stirred at 50° C. for 2 h. The mixture is diluted with saturated aqueous Na2CO3 (50 mL), and extracted with EtOAc (3×50 mL). The combined organic layer is dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 0%-7% MeOH in DCM to afford 4-methyl-2-thiazol-2-yl-pyrimidine-5-carboxylic acid [5-fluoro-3-(3-hydroxy-3-methyl-butyl)-indol-1-yl]-amide (155 mg, 26%). MS: 440 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 9.22 (s, 1H), 8.14 (d, 1H), 8.08 (d, 1H), 7.40 (m, 3H), 7.06 (m, 1H), 4.31 (s, OH, 1H), 2.76 (s, 3H), 2.71 (m, 2H), 1.77 (m, 2H), 1.20 (s, 6H). IC50=5 nM.

Workup

  1. extractionextracted with EtOAc (3×50 mL)
  2. dry with materialThe combined organic layer is dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue is purified by silica gel chromatography
  6. washeluting with 0%-7% MeOH in DCM

Sources & evidence

ORD record
ord-1a6834622a9143e0b08543838f9b447d
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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