N-methyl-2-pyrrolidone → 2-(4-Hydroxybicyclo[2.2.2]octan-1-ylamino)-4-(isopropylamino)-pyrimidine-5-carboxamide
Reaction equation
[CH:1]([NH:4][C:5]1[C:10]([C:11]([NH2:13])=[O:12])=[CH:9][N:8]=[C:7](S(C)=O)[N:6]=1)([CH3:3])[CH3:2].C(NC1C(C(N)=O)=CN=C(S(C)(=O)=O)N=1)(C)C.CN1C(=O)CCC1.Cl.[NH2:42][C:43]12[CH2:50][CH2:49][C:46]([OH:51])([CH2:47][CH2:48]1)[CH2:45][CH2:44]2.CCN(C(C)C)C(C)C>>[OH:51][C:46]12[CH2:49][CH2:50][C:43]([NH:42][C:7]3[N:6]=[C:5]([NH:4][CH:1]([CH3:3])[CH3:2])[C:10]([C:11]([NH2:13])=[O:12])=[CH:9][N:8]=3)([CH2:48][CH2:47]1)[CH2:44][CH2:45]2Participants
Reactant 5
Product 1
Conditions
- Temperature
- 100 °C
Procedure
To the solution of 4-(isopropylamino)-2-(methylsulfinyl)-pyrimidine-5-carboxamide and 4-(isopropylamino)-2-(methylsulfonyl)pyrimidine-5-carboxamide in NMP (from previous step, 2.8 mmol), 4-aminobicyclo[2.2.2]octan-1-ol hydrochloride (500 mg, 2.8 mmol), DIEA (1.1 g, 8.4 mmol) were added and heated at 100° C. for 3 d. The resulting mixture was concentrated under reduced pressure and the residue was purified by preparative thin layer chromatography to afford the final product (74.1 mg, 8.2% yield). 1H NMR (DMSO-d6) δ ppm 8.88 (br s, 1H), 8.31 (s, 1H), 7.5-6.5 (br s, 2H), 5.76 (s, 1H), 4:25 (s, 4.11 (brs, 1H), 2.05-1.97 (m, 6H), 1.61-1.54 (m, 6H), 1.24-1.12 (m, 6H); MS (ESI) m/z 320.2 [M+H]+; Purity=96.5% at 214 nm, Purity=97.7% at 254 nm.
Workup
- concentrationThe resulting mixture was concentrated under reduced pressure
- customthe residue was purified by preparative thin layer chromatography
Sources & evidence
- ORD record
- ord-834f0a2567b449cca233a1fdec078fb3
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09139534B2
Reaction notes
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