Triethylamine → HCID 135438360, compound

HRID 2062196Notes

Reaction equation

HRID 2062196 reaction equation
[F:1][C:2]1[C:3]([C:9]2[N:18]=[C:17]([N:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)[C:16]3[C:11](=[CH:12][C:13]([CH3:25])=[CH:14][CH:15]=3)[N:10]=2)=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.[OH:26][C@H:27]([CH2:31][C:32]([CH3:35])([CH3:34])[CH3:33])[C:28](O)=[O:29].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([OH:8])[C:3]=1[C:9]1[N:18]=[C:17]([N:19]2[CH2:24][CH2:23][N:22]([C:28](=[O:29])[C@H:27]([OH:26])[CH2:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:21][CH2:20]2)[C:16]2[C:11](=[CH:12][C:13]([CH3:25])=[CH:14][CH:15]=2)[N:10]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 9898860(R)-2-hydroxy-4,4-dimethylpentanoic acidHCID 1361214163-Fluoro-2-(7-methyl-4-(piperazin-1-yl)quinazolin-2-yl)phenol

Product 1

HCID 135438360HCID 135438360, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

3-Fluoro-2-(7-methyl-4-(piperazin-1-yl)quinazolin-2-yl)phenol (250 mg, 0.74 mmol) was suspended in anhydrous DMF (5 mL) and cooled to 0° C. (internal temperature). Under an N2 atmosphere, (R)-2-hydroxy-4,4-dimethylpentanoic acid (118.4 mg, 0.81 mmol) was added followed by triethylamine (0.207 mL, 1.48 mmol). To this stirring solution was added HATU (337 mg, 0.888 mmol). After the complete addition of HATU, the mixture was allowed to warm to 10° C. After 45 min the reaction was complete, and it was quenched with an equal portion of ice water. A yellow precipitate formed which was collected by vacuum filtration, dissolved in CH2Cl2, and the CH2Cl2 solution was desiccated with Na2SO4, filtered, and concentrated to a viscous yellow-orange oil. The crude material was purified via silica gel chromatography using 70% CH2Cl2/hexanes (1:1) and 30% EtOAc to afford (R)-1-(4-(2-(2-fluoro-6-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4,4-dimethylpentan-1-one as a yellow solid (171 mg, 50%). LC/MS: m/z 467.1 (M+H)+ at 2.63 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, DMSO-d6) δ 8.02 (d, J=8.6 Hz, 1H), 7.69 (s, 1H), 7.43 (dd, J=8.6, 1.5 Hz, 1H), 7.37-7.32 (m, 1H), 6.80 (d, J=8.3 Hz, 1H), 6.76-6.71 (m, 1H), 4.87 (d, J=7.2 Hz, 1H), 4.47-4.43 (m, 1H), 4.01-3.75 (m, 8H), 2.52 (s, 3H), 1.55 (dd, J=14.3, 3.0 Hz, 1H), 1.40 (dd, J=14.3, 8.8 Hz, 1H), 0.96 (s, 9H)

Workup

  1. temperatureto warm to 10° C
  2. customit was quenched with an equal portion of ice water
  3. customA yellow precipitate formed which
  4. filtrationwas collected by vacuum filtration
  5. dissolutiondissolved in CH2Cl2
  6. filtrationfiltered
  7. concentrationconcentrated to a viscous yellow-orange oil
  8. customThe crude material was purified via silica gel chromatography

Sources & evidence

ORD record
ord-1655365c64604a708ab675c04ff3b837
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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