Sulfuric Acid → HCID 86707829, compound

HRID 1747704Notes

Reaction equation

HRID 1747704 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:22]([C:24]3[O:25][C:26]4[C:31]([C:32](=[O:41])[C:33]=3[C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[CH:35]=3)=[CH:30][C:29]([F:42])=[CH:28][CH:27]=4)[CH3:23])[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH:18]([CH3:20])[CH3:19])=[C:13]([F:21])[CH:12]=3)[C:3]=12.[S:43](=[O:47])(=[O:46])([OH:45])[OH:44]>C(O)(C)C>[S:43]([OH:47])([OH:46])(=[O:45])=[O:44].[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:22]([C:24]3[O:25][C:26]4[C:31]([C:32](=[O:41])[C:33]=3[C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[CH:35]=3)=[CH:30][C:29]([F:42])=[CH:28][CH:27]=4)[CH3:23])[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH:18]([CH3:19])[CH3:20])=[C:13]([F:21])[CH:12]=3)[C:3]=12

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 72950888Umbralisib

Product 1

HCID 86707829HCID 86707829, compoundYield 76.8%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To (S)-2-(1-(4-amino-3-(3-fluoro-4-isopropoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-6-fluoro-3-(3-fluorophenyl)-4H-chromen-4-one (15.0 g, 26.24 mmol) in isopropanol (600 ml) was cooled to 0° C. To this Sulphuric acid (2.83 g, 28.86 mmol) was added and stirred at room temperature for 24 h. The reaction mass was filtered and washed with petroleum ether and dried under vacuum. To the solid, water (150 ml) was added and stirred for 30 min. The solid was filtered, washed with petroleum ether and dried under vacuum to afford the title compound as off-white solid (13.5 g, 76%). MP: 125-127° C. 1H-NMR (δ ppm, CDCl3, 400 MHz): 8.11 (s, 1H), 7.85 (dd, J=8.0, 3.0 Hz, 1H), 7.51 (dd, J=9.2, 4.2 Hz, 1H), 7.45-7.31 (m, 3H), 7.29 (m, 1H), 7.15 (t, J=8.3 Hz, 1H), 7.08 (dt, J=8.5, 2.4 Hz, 1H), 6.96 (br s, 1H), 6.88 (br s, 1H), 6.09 (q, J=7.1 Hz, 1H), 4.676 (quintet, J=6.1 Hz, 1H), 2.01 (d, J=7.1 Hz, 3H), 1.42 (d, J=6.1 Hz, 6H). Mass: 572.2 (M++1-H2SO4). Enantiomeric excess: 89.6% as determined by HPLC on a chiralpak AD-H column, enriched in the fast eluting isomer (retention time=12.08 min.)

Workup

  1. filtrationThe reaction mass was filtered
  2. washwashed with petroleum ether
  3. customdried under vacuum
  4. additionTo the solid, water (150 ml) was added
  5. stirringstirred for 30 min
  6. filtrationThe solid was filtered
  7. washwashed with petroleum ether
  8. customdried under vacuum

Sources & evidence

ORD record
ord-c72eba68d6cf4045bb69d45374558a7f
Source dataset
uspto-grants-2015_10
Patent number
US09150579B2

Reaction notes

Loading…