Aniline → HCID 86723980, compound

HRID 1475370Notes

Reaction equation

CC([O-])(C)C.[Na+].[NH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C(OC([N:21]1[CH2:26][CH2:25][N:24]([CH2:27][C:28]([N:30]2[C:38]3[C:33](=[CH:34][CH:35]=[C:36](Br)[CH:37]=3)[CH2:32][CH2:31]2)=[O:29])[CH2:23][C@H:22]1[CH3:40])=O)(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]>[CH3:40][C@H:22]1[NH:21][CH2:26][CH2:25][N:24]([CH2:27][C:28]([N:30]2[C:38]3[C:33](=[CH:34][CH:35]=[C:36]([NH:7][C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=4)[CH:37]=3)[CH2:32][CH2:31]2)=[O:29])[CH2:23]1

Participants

Conditions

Temperature: 100 °C

Procedure

To Pd2(dba)3 (4 mg, 0.005 mmol), (2-biphenyl)P(t-Bu)2 (1 mg, 0.005 mmol), and NaOtBu (31 mg, 0.32 mmol) was added a solution of the aniline (26 mg, 0.27 mmol) in toluene (0.57 mL), followed by (R)-4-[2-(6-bromo-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (50 mg, 0.11 mmol). The mixture was heated to 100° C. for 18 h then filtered and concentrated and the residue purified by preparative HPLC (TFA method), to give the title compound (12 mg, 24%) as a orange/brown solid. 1H NMR (Me-d3-OD): 8.05 (1H, dd), 7.30-7.17 (2H, m), 7.13 (1H, d), 7.10-7.02 (2H, m), 6.91-6.81 (2H, m), 4.58 (1H, s), 4.43-4.26 (2H, m), 4.26-4.16 (1H, m), 4.16-4.04 (2H, m), 3.71 (1H, d), 3.58-3.38 (2H, m), 3.29-3.18 (4H, m), 1.51 (9H, s), 1.43 (3H, d).

Workup

filtrationthen filtered
concentrationconcentrated
customthe residue purified by preparative HPLC (TFA method)

Sources & evidence

ORD record: ord-0a466afdc1f9422aa15372b2b22d57ef
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09018214B2

Reaction notes

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