Cesium carbonate → 4-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-2H-benzo[b][1,4]oxazin-3(4H)-one

HRID 2202658Notes

Reaction equation

[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[CH2:11][CH:12]([OH:26])[CH2:13][NH:14][C:15](=[O:25])[CH2:16][O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1I.C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.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]>[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[CH2:11][CH:12]([OH:26])[CH2:13][N:14]1[C:15](=[O:25])[CH2:16][O:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]1=2

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-2-(2-iodophenoxy)acetamide (100 mg, 0.215 mmol) in dioxane (5 mL) was added Cs2CO3 (139 mg, 0.429 mmol), BINAP (13.3 mg, 0.0215 mmol) and Pd2(dba)3 (8.0 mg, 0.0215 mmol). The reaction mixture was heated at 120° C. for 16 h, cooled to room temperature, filtered, and concentrated. The crude produce was purified by preparative HPLC purification. (23.6 mg, yield 32.5%) MS (ESI+) e/z: 339.2 [M+1]+. 1H NMR (MeOD, 400 MHz), δ ppm: 7.41-7.32 (m, 1H), 7.15-7.06 (m, 3H), 7.06-6.94 (m, 4H), 4.67-4.50 (m, 2H), 4.29-4.13 (m, 2H), 4.07-3.94 (m, 1H), 3.77-3.64 (m, 2H), 2.95-2.83 (m, 3H), 2.83-2.76 (m, 1H), 2.73-2.62 (m, 2H).

Workup

temperaturecooled to room temperature
filtrationfiltered
concentrationconcentrated
customThe crude produce
customwas purified by preparative HPLC purification

Sources & evidence

ORD record: ord-9bd096686a3e4d7695ce07bb57e6437c
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365555B2

Reaction notes

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