Reaction equation
O[N:2]1[C:11]2[C:10]3[CH:12]=[CH:13][N:14]=[CH:15][C:9]=3[NH:8][C:7]3[N:16]=[CH:17][CH:18]=[CH:19][C:6]=3[C:5]=2[N:4]=[C:3]1[CH:20]1[CH2:25][CH2:24][CH:23]([CH2:26][C:27]#[N:28])[CH2:22][CH2:21]1.P(OC(C)C)(OC(C)C)OC(C)C>CN(C)C(=O)C>[N:4]1[C:5]2[C:6]3[CH:19]=[CH:18][CH:17]=[N:16][C:7]=3[NH:8][C:9]3[CH:15]=[N:14][CH:13]=[CH:12][C:10]=3[C:11]=2[NH:2][C:3]=1[CH:20]1[CH2:21][CH2:22][CH:23]([CH2:26][C:27]#[N:28])[CH2:24][CH2:25]1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of [4-(3-hydroxy-3,8-dihydroimidazo[4,5-d]dipyrido[2,3-b:4′,3′-f]azepin-2-yl)cyclohexyl]acetonitrile (7.0 g, 0.019 mol) and triisopropyl phosphite (20 mL, 0.08 mol) in N,N-dimethylacetamide (20 mL) was heated at 160° C. for 2 hours and was then concentrated in vacuo. The residue was purified by column chromatography on silica gel (5% trimethylamine 7.5% methanol and 87.5% ethyl acetate) yielding 4.10 g of product as a 9:1 mixture of the two diastereomers. The pure cis and trans isomers could be obtained by preparative HPLC. 1H NMR (300, DMSO-d6): δ 12.73 and 12.01 (br s, 1H), 7.83-7.99 (m, 4H), 7.70 and 7.46 (m, 1H), 6.77 (m, 1H), 2.54-2.63 (m, 1H), 2.49 (m, 2H), 1.84-2.02 (m, 4H), 1.50-1.79 (m, 3H), 1.09-1.24 (m,2H).
Workup
- concentrationwas then concentrated in vacuo
- customThe residue was purified by column chromatography on silica gel (5% trimethylamine 7.5% methanol and 87.5% ethyl acetate)
Sources & evidence
- ORD record
- ord-60dd0d3ac65b4bd58bc7384c0ad46dbe
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08835423B2
Linked notes
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