4-Aminopyrimidine → 4-(4-cyano-2-methoxyphenyl)-N-(pyrimidin-4-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

HRID 528645Notes

Reaction equation

[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][O:12][C:11]3[CH:15]=[C:16]([S:19](OC4C(F)=C(F)C(F)=C(F)C=4F)(=[O:21])=[O:20])[CH:17]=[CH:18][C:10]2=3)=[C:5]([O:34][CH3:35])[CH:4]=1)#[N:2].[NH2:36][C:37]1[CH:42]=[CH:41][N:40]=[CH:39][N:38]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][O:12][C:11]3[CH:15]=[C:16]([S:19]([NH:36][C:37]4[CH:42]=[CH:41][N:40]=[CH:39][N:38]=4)(=[O:20])=[O:21])[CH:17]=[CH:18][C:10]2=3)=[C:5]([O:34][CH3:35])[CH:4]=1)#[N:2]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of perfluorophenyl 4-(4-cyano-2-methoxyphenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonate (180 mg, 0.351 mmol) and 4-amino pyrimidine (50 mg, 0.527 mmol) in THF (5 mL) was added LiHMDS (1M in THF, 0.7 mL, 0.703 mmol) at −78° C. The reaction mixture was stirred at same temperature for 5 minutes and at 0° C. for 1 h. After completion, reaction mixture was quenched with 2-3 drops of acetic acid and concentrated under reduced pressure. The crude mass was purified by prep purification to obtain 4-(4-cyano-2-methoxyphenyl)-N-(pyrimidin-4-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (13 mg, 11.3%) as a white solid. m/z (ESI) 423.0 (M+H)+. 1H NMR (400 MHz, DMSO) δ 11.88 (s, 1H), 8.64 (s, 1H), 8.36 (d, J=5.8 Hz, 1H), 7.65 (s, 1H), 7.55-7.43 (m, 2H), 7.35-7.15 (m, 2H), 7.00 (d, J=5.9 Hz, 1H), 6.34 (d, J=8.6 Hz, 1H), 4.30 (t, J=4.0 Hz, 2H), 3.81 (s, 3H), 3.67-3.65 (m, 2H).

Workup

customAfter completion, reaction mixture
customwas quenched with 2-3 drops of acetic acid
concentrationconcentrated under reduced pressure
customThe crude mass was purified by prep purification

Sources & evidence

ORD record: ord-88a41c081ff341d0b9bd1357a8a96ba7
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346798B2

Reaction notes

Loading…