(2S)-1-amino-3-(1,3-dihydroisoindol-2-yl)propan-2-ol → (R)-N-((S)-2-hydroxy-3-(isoindolin-2-yl)propyl)-2-(quinolin-8-yloxy)propanamide

HRID 1507018Notes

Reaction equation

[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[O:11][C@H:12]([CH3:17])[C:13]([O:15]C)=O)[CH:4]=[CH:3][CH:2]=1.[NH2:18][CH2:19][C@H:20]([OH:31])[CH2:21][N:22]1[CH2:30][C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23]1>CCO>[OH:31][C@H:20]([CH2:21][N:22]1[CH2:23][C:24]2[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:30]1)[CH2:19][NH:18][C:13](=[O:15])[C@H:12]([O:11][C:9]1[CH:8]=[CH:7][CH:6]=[C:5]2[C:10]=1[N:1]=[CH:2][CH:3]=[CH:4]2)[CH3:17]

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of (R)-methyl 2-(quinolin-8-yloxy)propanoate (100 mg, 0.433 mmol) in EtOH (1 mL) was added (S)-1-amino-3-(isoindolin-2-yl)propan-2-ol (83 mg, 0.433 mmol). The reaction mixture was heated under microwave conditions at 120° C. for 0.5 h. The mixture was concentrated and purified by preparative HPLC purification. (15 mg, yield 8.8%) MS (ESI+) e/z: 392.1 [M+1]+. 1H NMR (MeOD, 400 MHz), δ ppm: 1H NMR (400 MHz, METHANOL-d4) δ 8.90 (dd, J=4.27, 1.76 Hz, 1H) 8.33 (dd, J=8.41, 1.63 Hz, 1H) 7.51-7.64 (m, 3H) 7.29 (dd, J=6.15, 2.64 Hz, 1H) 7.08-7.22 (m, 4H) 5.08 (q, J=6.78 Hz, 1H) 3.75-3.93 (m, 5H) 3.36-3.43 (m, 2H) 2.55-2.66 (m, 2H) 1.73 (d, J=6.78 Hz, 3H).

Workup

concentrationThe mixture was concentrated
custompurified by preparative HPLC purification

Sources & evidence

ORD record: ord-8bb0e35897694c7f9453a7b06253e54b
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09221794B2

Reaction notes

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