4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride → 4-Methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid [5-fluoro-3-(3-hydroxy-3-methyl-butyl)-indol-1-yl]-amide

HRID 2382044Notes

Reaction equation

HRID 2382044 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:12]=[C:11]([CH3:13])[C:10]([C:14]([OH:16])=O)=[CH:9][N:8]=1.[NH2:17][N:18]1[C:26]2[C:21](=[CH:22][C:23]([F:27])=[CH:24][CH:25]=2)[C:20]([CH2:28][CH2:29][C:30]([CH3:33])([OH:32])[CH3:31])=[CH:19]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:27][C:23]1[CH:22]=[C:21]2[C:26](=[CH:25][CH:24]=1)[N:18]([NH:17][C:14]([C:10]1[C:11]([CH3:13])=[N:12][C:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)=[N:8][CH:9]=1)=[O:16])[CH:19]=[C:20]2[CH2:28][CH2:29][C:30]([OH:32])([CH3:31])[CH3:33]

Participants

6

Reactant 3

HCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 617020254-Methyl-2-(pyridin-2-yl)pyrimidine-5-carboxylic acidHCID 685521584-(1-amino-5-fluoro-1H-indol-3-yl)-2-methyl-butan-2-ol

Product 1

HCID 592000274-Methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid [5-fluoro-3-(3-hydroxy-3-methyl-butyl)-indol-1-yl]-amideYield 44%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 2-(2-pyridyl)-4-methyl-pyrimidine-5-carboxylic acid (516 mg, 4 mmol) and 4-(1-amino-5-fluoro-1H-indol-3-yl)-2-methyl-butan-2-ol (566 mg, 4 mmol) in DMF (5 mL) is stirred at 50° C. for 1 h. The mixture is treated with DMTMM (662 mg, 4 mmol) and stirred at 50° C. for 1 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 4%-10% MeOH in DCM to afford 4-methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid [5-fluoro-3-(3-hydroxy-3-methyl-butyl)-indol-1-yl]-amide (450 mg, 44%). MS: 434 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 9.25 (s, 1H), 8.81 (d, 1H), 8.47 (d, 1H), 8.02 (m, 1H), 7.58 (m, 1H), 7.43 (m, 3H), 7.06 (m, 1H), 4.29 (s, OH, 1H), 2.78 (s, 3H), 2.72 (m, 2H), 1.77 (m, 2H), 120 (s, 6H).

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 4%-10% MeOH in DCM

Sources & evidence

ORD record
ord-cbeff5eccbdd449182aa58d22944fae9
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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