Chlorotrimethylsilane → HCID 59518985, compound

HRID 1161871Notes

Reaction equation

HRID 1161871 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5](Cl)=O.[NH2:11][C:12]1[CH:28]=[CH:27][C:26]([N:29]2[CH2:35][CH2:34][CH2:33][N:32]([CH:36]([CH3:38])[CH3:37])[CH2:31][CH2:30]2)=[CH:25][C:13]=1[C:14]([NH:16][CH2:17][C:18](=[O:24])[NH:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:15].C(N(CC)CC)C.C[Si](Cl)(C)C>C(Cl)Cl>[C:20]([NH:19][C:18](=[O:24])[CH2:17][N:16]1[C:14](=[O:15])[C:13]2[C:12](=[CH:28][CH:27]=[C:26]([N:29]3[CH2:35][CH2:34][CH2:33][N:32]([CH:36]([CH3:38])[CH3:37])[CH2:31][CH2:30]3)[CH:25]=2)[N:11]=[C:5]1[C:4]1[CH:8]=[CH:9][CH:10]=[C:2]([F:1])[CH:3]=1)([CH3:23])([CH3:22])[CH3:21]

Participants

6

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 743763-Fluorobenzoyl chlorideHCID 67415466HCID 67415466, compound2×

Product 1

HCID 59518985HCID 59518985, compoundYield 7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
150 °C

Procedure

3-Fluorobenzoyl chloride (24 mg, 0.154 mmol, 0.019 mL) was added to an ice-water cooled solution of 2-amino-N-(tert-butylcarbamoylmethyl)-5-(4-isopropylperhydro-1,4-diazepin-1-yl)benzamide (INTERMEDIATE V.49) (60 mg, 0.154 mmol) and triethylamine (716 mg, 0.96 mL, 7.09 mmol) in DCM (2 mL). Stirring was continued for 15 min. Trimethylsilyl chloride (251 mg, 0.295 mL, 2.31 mmol) was added and the reaction mixture heated in the microwave at 150° C. for 7 min. The reaction mixture was diluted with DCM (10 mL) and washed with water. The organic phase was dried (MgSO4) and concentrated in vacuo. Crude product was purified by chromatography on silica gel with a gradient of DCM to DCM:MeOH:NH3 (95:4:1, v/v) as eluent. Further purification by preparative HPLC afforded N-tert-butyl-2-[2-(3-fluorophenyl)-6-(4-isopropylperhydro-1,4-diazepin-1-yl)-4-oxo-4H-quinazolin-3-yl]acetamide (EXAMPLE 7d) (5 mg, 10 μmol, 7%).

Workup

  1. washwashed with water
  2. dry with materialThe organic phase was dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customCrude product was purified by chromatography on silica gel with a gradient of DCM to DCM:MeOH:NH3 (95:4:1
  5. customFurther purification by preparative HPLC

Sources & evidence

ORD record
ord-4b09bbd2aa7545cab564ca76d952203f
Source dataset
uspto-grants-2010_10
Patent number
US07820649B2

Reaction notes

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