Triethylamine → HCID 59380395, compound

HRID 2353837Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:19]3[C:26]4[CH:27]=[CH:28][C:29]([OH:31])=[CH:30][C:25]=4[S:24][C:20]=3[N:21]=[CH:22][N:23]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.[CH2:32]1[O:34][C@@H:33]1[CH2:35][OH:36].C(N(CC)CC)C>CCO>[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:19]3[C:26]4[CH:27]=[CH:28][C:29]([O:31][CH2:32][C@H:33]([OH:34])[CH2:35][OH:36])=[CH:30][C:25]=4[S:24][C:20]=3[N:21]=[CH:22][N:23]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 4-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)[1]benzothieno[2,3-d]pyrimidin-7-ol (30 mg, 0.07 mmol) in EtOH (1.0 mL) was added (R)-(+)-glycidol (5 mg, 0.07 mL, 1.0 equiv) and triethylamine (0.34 mg, 0.0035 mmol, 0.05 equiv) under nitrogen. The reaction mixture was stirred at 80° C. for 15 h and then cooled to rt. The solvents were removed in vacuo. The residue was purified by preparative HPLC to afford (2R)-3-{[4-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)[1]benzothieno[2,3-d]pyrimidin-7-yl]oxy}propane-1,2-diol as a white solid (14.8 mg, 40%). 1H-NMR (CD3OD) δ 8.45 (s, 1H), 8.32 (d, J=8.9 Hz, 1H), 7.73 (d, J=2.7 Hz, 1H), 7.61 (d, J=2.2 Hz, 1H), 7.46 (dd, J=2.7, 9.0 Hz, 1H), 7.40 (m, 1H), 7.30 (d, J=7.8 Hz, 1H), 7.25 (dd, J=2.3, 9.0 Hz, 2H), 7.16 (d, J=9 Hz, 1H), 7.05 (td, 1H), 5.22 (s, 2H), 4.20 (m, 1H), 4.11 (m, 1H), 4.04 (m, 1H), 3.72 (m, 2H), LCMS RT=3.32 min, [M+H]+=526.1.

Workup

temperaturecooled to rt
customThe solvents were removed in vacuo
customThe residue was purified by preparative HPLC

Sources & evidence

ORD record: ord-ba90d51ac70b4fbb900818a20af79c50
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07750017B2

Reaction notes

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