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

HRID 2382043Notes

Reaction equation

HRID 2382043 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([CH3:14])[C:11]([C:15]([OH:17])=O)=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.[NH2:18][N:19]1[C:27]2[C:22](=[CH:23][C:24]([F:28])=[CH:25][CH:26]=2)[C:21]([CH2:29][CH2:30][C:31]([CH3:34])([OH:33])[CH3:32])=[CH:20]1.C[N+]1(C2N=C(OC)N=C(OC)N=2)CCOCC1.[Cl-]>CN(C=O)C>[F:28][C:24]1[CH:23]=[C:22]2[C:27](=[CH:26][CH:25]=1)[N:19]([NH:18][C:15]([C:11]1[C:12]([CH3:14])=[N:13][C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)=[N:9][CH:10]=1)=[O:17])[CH:20]=[C:21]2[CH2:29][CH2:30][C:31]([OH:33])([CH3:32])[CH3:34]

Participants

5

Reactant 3

HCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 617025872-(3-Fluorophenyl)-4-methylpyrimidine-5-carboxylic acidHCID 685521584-(1-amino-5-fluoro-1H-indol-3-yl)-2-methyl-butan-2-ol

Product 1

HCID 591999452-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid [5-fluoro-3-(3-hydroxy-3-methyl-butyl)-indol-1-yl]-amideYield 61%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (278 mg, 1.2 mmol) and 4-(1-amino-5-fluoro-1H-indol-3-yl)-2-methyl-butan-2-ol (1.2 mmol) in DMF (10 mL) is stirred at 50° C. for 1 h. The mixture is treated with DMTMM (331 mg, 1.2 mmol) and stirred at 50° C. for 1 h. The mixture is concentrated in vacuo, 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 50% EtOAc in heptane to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid [5-fluoro-3-(3-hydroxy-3-methyl-butyl)-indol-1-yl]-amide (330 mg, 61%). MS: 451 (M+H); 1H NMR (300 MHz, CD3OD): δ 9.10 (s, 1H), 8.36 (d, 1H), 8.23 (d, 1H), 7.55 (m, 1H), 7.32 (m, 3H), 7.18 (s, 1H), 7.03 (m, 1H), 3.91 (s, OH, 1H), 2.84 (s, 3H), 2.82 (m, 2H), 1.91 (m, 2H), 1.31 (s, 6H).

Workup

  1. concentrationThe mixture is concentrated in vacuo
  2. additiondiluted with saturated aqueous Na2CO3 (50 mL)
  3. extractionextracted with EtOAc (3×50 mL)
  4. dry with materialThe combined organic layer is dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by silica gel chromatography
  8. washeluting with 50% EtOAc in heptane

Sources & evidence

ORD record
ord-881bb0ab891d425b9b2b4b6b4c628a38
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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