4-Tert-Butylaniline → HCID 24782891, compound

HRID 1485341Notes

Reaction equation

HRID 1485341 reaction equation
Cl[C:2]1[C:12]2[CH2:11][CH2:10][N:9]([C:13]3[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:16]=[CH:15][N:14]=3)[CH2:8][CH2:7][C:6]=2[N:5]=[CH:4][N:3]=1.[C:23]([C:27]1[CH:33]=[CH:32][C:30]([NH2:31])=[CH:29][CH:28]=1)([CH3:26])([CH3:25])[CH3:24]>CCCCO>[C:23]([C:27]1[CH:28]=[CH:29][C:30]([NH:31][C:2]2[C:12]3[CH2:11][CH2:10][N:9]([C:13]4[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:16]=[CH:15][N:14]=4)[CH2:8][CH2:7][C:6]=3[N:5]=[CH:4][N:3]=2)=[CH:32][CH:33]=1)([CH3:26])([CH3:24])[CH3:25]

Participants

4

Reactant 2

HCID 698614-Tert-ButylanilineHCID 58972713HCID 58972713, compound

Product 1

HCID 24782891HCID 24782891, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

To a solution of 4-chloro-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine (27 mg, 0.085 mmol) in n-BuOH (1 mL) was added 4-tert-butylaniline (27 μL, 0.17 mmol). After 2 h at 135° C., the mixture was cooled to rt, quenched with saturated aqueous (satd. aq.) NaHCO3, and extracted with EtOAc. The combined organic layers were dried (Na2SO4) and concentrated. The residue was purified (FCC) to give the title compound (33 mg, 89%). MS (ESI): mass calcd. for C24H26F3N5, 441.21; m/z found, 442.2 [M+H]+. 1H NMR (CDCl3): 8.50 (s, 1H), 8.40-8.37 (m, 1H), 7.90-7.85 (m, 1H), 7.46-7.36 (m, 4H), 6.98-6.93 (m, 1H), 6.45 (s, 1H), 3.70-3.65 (m, 2H), 3.64-3.60 (m, 2H), 3.26-3.20 (m, 2H), 3.02-2.95 (m, 2H), 1.32 (s, 9H). Alternatively, the reaction of this step may be performed in the microwave at 180° C. for 30 min.

Workup

  1. customquenched with saturated aqueous (satd. aq.) NaHCO3
  2. extractionextracted with EtOAc
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was purified (FCC)

Sources & evidence

ORD record
ord-22bf88211e24429e9f9789b213d2190c
Source dataset
uspto-grants-2016_08
Patent number
US09422293B2

Reaction notes

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