Toluene → HCID 67342163, compound

HRID 451532Notes

Reaction equation

HRID 451532 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:14][CH2:13][CH2:12][N:11]3[N:15]=[C:16]([NH2:18])[N:17]=[C:10]23)[CH:5]=[CH:6][C:7]=1[F:8].C(N(CC)CC)C.CP(C)C.C1(C)C=CC=CC=1.[CH3:37][C:38]1[N:43]=[CH:42][N:41]=[C:40]([N:44]2[CH2:49][CH2:48][C:47](=O)[CH2:46][CH2:45]2)[CH:39]=1.C(Cl)Cl>O1CCCC1.O>[F:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:14][CH2:13][CH2:12][N:11]3[N:15]=[C:16]([NH:18][CH:47]4[CH2:48][CH2:49][N:44]([C:40]5[CH:39]=[C:38]([CH3:37])[N:43]=[CH:42][N:41]=5)[CH2:45][CH2:46]4)[N:17]=[C:10]23)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

9

Reactant 6

HCID 1140TolueneHCID 6344DichloromethaneHCID 8471TriethylamineHCID 68983TrimethylphosphineHCID 61226887HCID 61226887, compoundHCID 67336132HCID 67336132, compound

Product 1

HCID 67342163HCID 67342163, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-(3,4-difluorophenyl)-4,5,6,7-tetrahydro-[1,2,4]triazolo[1,5-a]pyrimidin-2-amine (41 mg, 163 μmol) in tetrahydrofurane (1 mL) was added under an atmosphere of nitrogen hexachloroethane (61.0 mg, 245 μmol), triethylamine (49.5 mg, 68.2 μL, 490 μmol) and a 1 M solution of trimethylphosphine in toluene (245 μL, 245 μmol). The suspension was stirred for 30 minutes at room temperature. 1-(6-Methylpyrimidin-4-yl)piperidin-4-one (see example 93b, 46.8 mg, 245 μmol) dissolved in tetrahydrofurane (0.5 mL) was added and the yellow suspension was heated to 150° C. for 30 minutes. A 1 M solution of borane tetrahydrofurane complex in methylene chloride (490 μL, 490 μmol) was added and the reaction was heated to 100° C. for one hour. The reaction was diluted with water and extracted twice with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and the solvent was evaporated. The title compound was obtained as a colorless solid (14 mg, 20%) after column chromatography on silica gel using a gradient from methylene chloride to methylene chloride/methanol 19:1 (v/v) as eluent and subsequent purification with preparative HPCL. MS ISP (m/e): 427.3 (100) [(M+H)+], 176.3 (81).

Workup

  1. additionwas added
  2. temperaturethe yellow suspension was heated to 150° C. for 30 minutes
  3. temperaturethe reaction was heated to 100° C. for one hour
  4. extractionextracted twice with ethyl acetate
  5. washThe combined organic layers were washed with saturated aqueous sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customthe solvent was evaporated

Sources & evidence

ORD record
ord-e9727c6ed04c482e871b2fee00f5bfb2
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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