Diisopropylamine → HCID 79075584, compound

HRID 1850112Notes

Reaction equation

HRID 1850112 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([F:9])=[CH:4][N:3]=1.C(NC(C)C)(C)C.[NH2:17][CH2:18][C:19]([CH3:22])([OH:21])[CH3:20]>C(#N)C>[Cl:1][C:2]1[N:7]=[C:6]([NH:17][CH2:18][C:19]([CH3:22])([OH:21])[CH3:20])[C:5]([F:9])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 7912DiisopropylamineHCID 951022-Propanol, 1-amino-2-methyl-HCID 2507052,4-Dichloro-5-fluoropyrimidine

Product 1

HCID 79075584HCID 79075584, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 2,4-dichloro-5-fluoropyrimidine (2 g, 11.98 mmol) in acetonitrile (10 mL) was cooled to −40° C., avoiding freezing. To this solution was added diisopropylamine (3.82 mL, 21.88 mmol) followed by 1-amino-2-methylpropan-2-ol (1.5 g, 16.83 mmol). The reaction mixture was removed from the cooling bath, warmed to room temperature and allowed to stir overnight (˜18 hours). Solvents were removed in vacuo and the residue was taken up in a minimum of dichloromethane (˜1.5-2 mL) and diluted with heptane until slightly cloudy. This mixture was loaded onto a 40 gram BioRad silica gel cartridge. Purification by flash chromatography (Analogix System, 20 min gradient, 0-25% methanol/dichloromethane, 40 mL/min.) provided 1-(2-chloro-5-fluoropyrimidin-4-ylamino)-2-methylpropan-2-ol as a white solid. LCMS m/z 220.1, 221.8 (M+H)+, Rt 0.49 min.

Workup

  1. customThe reaction mixture was removed from the cooling bath
  2. customSolvents were removed in vacuo
  3. additiondiluted with heptane until slightly cloudy
  4. customPurification by flash chromatography (Analogix System, 20 min gradient, 0-25% methanol/dichloromethane, 40 mL/min.)

Sources & evidence

ORD record
ord-034c007300c141de854b8d225e9c5b8f
Source dataset
uspto-grants-2015_02
Patent number
US08957068B2

Reaction notes

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