Hydrochloric Acid → (R)-5-(5-(1-amino-2,3-dihydro-1H-inden-4-yl)oxazol-2-yl)-2-isopropoxybenzonitrile hydrochloride

HRID 1053759Notes

Reaction equation

[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[O:14][C:15]([C:18]3[CH:26]=[CH:25][CH:24]=[C:23]4[C:19]=3[CH2:20][CH2:21][C@H:22]4[NH:27]C(=O)OC(C)(C)C)=[CH:16][N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2].[ClH:35]>O1CCOCC1.CCOCC>[ClH:35].[NH2:27][C@H:22]1[C:23]2[C:19](=[C:18]([C:15]3[O:14][C:13]([C:5]4[CH:6]=[CH:7][C:8]([O:9][CH:10]([CH3:12])[CH3:11])=[C:3]([CH:4]=4)[C:1]#[N:2])=[N:17][CH:16]=3)[CH:26]=[CH:25][CH:24]=2)[CH2:20][CH2:21]1

Participants

Conditions

Temperature: 60 °C

Procedure

To a stirring solution of (R)-tert-butyl 4-(2-(3-cyano-4-isopropoxyphenyl)oxazol-5-yl)-2,3-dihydro-1H-inden-1-ylcarbamate INT-42 (48 mg, 0.1 mmol) in 1,4-dioxane (1 mL) was added a 4N HCl solution in 1,4-dioxane (1 mL). The reaction mixture was heated at 55-65° C. for 48 h. The cooled reaction mixture was diluted with Et2O (10 mL). The resulting solid was collected and dried under high vacuum to yield 32 mg (78%) of (R)-5-(5-(1-amino-2,3-dihydro-1H-inden-4-yl)oxazol-2-yl)-2-isopropoxybenzonitrile hydrochloride 59 as a white solid. LCMS-ESI (m/z) calculated for C22H21N3O2: 359.4; found 343.1 [M−NH2]+, tR=2.40 min. 1H NMR (400 MHz, DMSO) δ 8.55 (br s, 2H), 8.43 (dd, J=6.5, 2.4 Hz, 1H), 8.32 (ddd, J=6.7, 6.1, 2.9 Hz, 1H), 8.00 (t, J=13.5 Hz, 1H), 7.72 (s, 1H), 7.66 (d, J=7.5 Hz, 1H), 7.49 (dd, J=8.5, 6.3 Hz, 2H), 4.93 (dt, J=12.1, 6.0 Hz, 1H), 4.81 (s, 1H), 3.43-3.25 (m, 1H), 3.23-3.04 (m, 1H), 2.67-2.55 (m, 1H), 2.11 (ddd, J=14.2, 9.0, 5.9 Hz, 1H), 1.36 (dd, J=13.8, 7.0 Hz, 6H).

Workup

customThe cooled reaction mixture
customThe resulting solid was collected
customdried under high vacuum

Sources & evidence

ORD record: ord-1fd18ee8269c469493ddcdbb3d45f88b
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394264B2

Reaction notes

Loading…