Ceralasertib → (S)-Ceralasertib

HRID 1038899Notes

Reaction equation

HRID 1038899 reaction equation
[CH3:1][C@@H:2]1[CH2:7][O:6][CH2:5][CH2:4][N:3]1[C:8]1[CH:13]=[C:12]([C:14]2([S@:17]([CH3:20])(=[NH:19])=[O:18])[CH2:16][CH2:15]2)[N:11]=[C:10]([C:21]2[CH:26]=[CH:25][N:24]=[C:23]3[NH:27][CH:28]=[CH:29][C:22]=23)[N:9]=1>CC(OC)(C)C>[CH3:1][C@@H:2]1[CH2:7][O:6][CH2:5][CH2:4][N:3]1[C:8]1[CH:13]=[C:12]([C:14]2([S@@:17]([CH3:20])(=[NH:19])=[O:18])[CH2:16][CH2:15]2)[N:11]=[C:10]([C:21]2[CH:26]=[CH:25][N:24]=[C:23]3[NH:27][CH:28]=[CH:29][C:22]=23)[N:9]=1

Participants

3

Reactant 1

HCID 54761306Ceralasertib

Product 1

HCID 54761305(S)-CeralasertibYield 69%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Procedure

4-{4-[(3R)-3-Methylmorpholin-4-yl]-6-[1-((R)—S-methylsulfonimidoyl)cyclopropyl]pyrimidin-2-yl}-1H-pyrrolo[2,3-b]pyridine (approximately 10 g, 25 mmol) was suspended in MTBE (500 ml) and stirred at reflux for 2 hours. The suspension was allowed to cool slowly and stirred at RT overnight. The solid was collected by filtration and dried under vacuum to afford the title compound (7.12 g) as a white crystalline solid; 1H NMR (400 MHz, DMSO-d6) 1.28 (3H, d), 1.44 (1H, dd), 1.47-1.58 (2H, m), 1.76 (1H, dt), 3.11 (3H, s), 3.26 (1H, dd), 3.52 (1H, td), 3.67 (1H, dd), 3.81 (1H, d), 3.85 (1H, d), 4.02 (1H, dd), 4.20 (1H, d), 4.59 (1H, s), 7.00 (1H, s), 7.23 (1H, dd), 7.57-7.62 (1H, m), 7.95 (1H, d), 8.34 (1H, d), 11.81 (1H, s); m/z: (ES+) MH+, 413.12. Mpt. (Buchi Melting Point B-545) 222° C. Chiral HPLC: (HP1100 System 7, 5 μm Chiralcel OJ (250 mm×4.6 mm) column eluting with Heptane/(EtOH/MeOH 50/50)/TEA 50/50/0.1) Rf, 9.836 99.8%.

Workup

  1. temperatureat reflux for 2 hours
  2. temperatureto cool slowly
  3. stirringstirred at RT overnight
  4. filtrationThe solid was collected by filtration
  5. customdried under vacuum

Sources & evidence

ORD record
ord-ea743bc8c78144f3aebadbd1cfa40d00
Source dataset
uspto-grants-2013_10
Patent number
US08552004B2

Reaction notes

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