4-Tert-Butylaniline → HCID 24782891, compound

HRID 1186112Notes

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

Conditions

Temperature: 135 °C

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 hat 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

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

Sources & evidence

ORD record: ord-7518a9c209e84934b6ea9abe742d3dde
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08673895B2

Reaction notes

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