tert-Butyl carbamate → HCID 67269196, compound

HRID 749853Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[N:14]([CH2:18][C:19]3[CH:24]=[CH:23][C:22](Br)=[CH:21][CH:20]=3)[N:13]=[C:12]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=3)[C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:33](=[O:40])([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[NH2:34].O.O.O.[O-]C1C=CC=CC=1.[Na+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[N:14]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([NH:34][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:40])=[CH:21][CH:20]=3)[N:13]=[C:12]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=3)[C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 1-(4-bromo-benzyl)-3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 113; 0.04 mmol), tert-butyl carbamate (0.05 mmol), sodium phenoxide trihydrate (0.05 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.001 mmol), and tri-tert-butylphosphine (0.05 mmol) in anhydrous toluene (3 mL) was heated under N2 at 100° C. for 6 h, 70° C. for 15 h and 100° C. for 2.5 h. After cooling to RT, the reaction mixture was purified directly by preparative TLC (2:1 hexanes/EtOAc) to yield 0.008 g of 1-(4-tert-butoxycarbonylamino-benzyl)-3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester, which was then diluted with DMF (1 mL) and treated with NaH (60%, 1.5 equiv.). After 15 min, methyl iodide (1.5 equiv.) was added. After 1 h, the reaction was quenched with H2O and the mixture was extracted with EtOAc (2×). The combined organic layers were dried over Na2SO4 and concentrated. The resulting semi-solid was then dissolved in CH2Cl2/MeOH (9:1, 1 mL) and treated with HCl (1 N in Et2O, 4 mL). The mixture was stirred at RT for 3 h, then was concentrated. The resulting oil was purified by preparative TLC (10% 2 M NH3 in MeOH/CH2Cl2) to yield 0.002 mg of the title compound as a white solid. MS (ESI): exact mass calculated for C21H23ClN4, 366.16; found, m/z 367.1 [M+H]+. 1H NMR (500 MHz, CD3OD): 7.39-7.32 (m, 4H), 6.84 (d, J=8.6 Hz, 1H), 6.48-6.45 (m, 2H), 5.12 (s, 2H), 2.84-2.81 (m, 4H), 2.79-2.77 (m, 2H), 2.69-2.66 (m, 2H), 2.63 (s, 3H).

Workup

temperatureAfter cooling to RT
customthe reaction mixture was purified directly by preparative TLC (2:1 hexanes/EtOAc)

Sources & evidence

ORD record: ord-614992f9051e4481bbf218a135c07b54
Source dataset: uspto-grants-2008_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07402680B2

Reaction notes

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