Water → HCID 178522505, compound

HRID 536257Notes

Reaction equation

[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:7]([CH2:21][CH2:22][N:23]=3)[C:8]([NH:12][C:13](=[O:20])[C:14]3[CH:19]=[CH:18][CH:17]=[N:16][CH:15]=3)=[N:9][C:10]=2[CH:11]=1.C([O-])([O-])=O.[K+].[K+].Cl[CH2:31][CH2:32][CH2:33][S:34]([N:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1)(=[O:36])=[O:35].O>CN(C=O)C>[N:37]1([S:34]([CH2:33][CH2:32][CH2:31][O:1][C:2]2[CH:3]=[CH:4][C:5]3[C:6]4[N:7]([CH2:21][CH2:22][N:23]=4)[C:8]([NH:12][C:13](=[O:20])[C:14]4[CH:19]=[CH:18][CH:17]=[N:16][CH:15]=4)=[N:9][C:10]=3[CH:11]=2)(=[O:36])=[O:35])[CH2:38][CH2:39][O:40][CH2:41][CH2:42]1

Participants

Conditions

Temperature: 120 °C

Procedure

To N-(8-hydroxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)nicotinamide (Example 2-5 in WO2004029055, 250 mg, 0.001 mol) and K2CO3 (1.1 g, 0.008 mol) in DMF (5 ml) was added 4-[(3-chloropropyl)sulfonyl]morpholine (Intermediate E, 204.0 mg, 0.001 mol) to a sealed tube and heated to 120° C. for 3 h. The reaction was poured into water and extracted with CH2Cl2. Organic layers dried with MgSO4, filtered and concentrated. The residue was purified using silica gel flash chromatography (100% EtOAc, then 0-20% MeOH/CH2Cl2) to provide the title compound (130 mg, 33%). TLC: Rf=0.21 in 10% MeOH/CH2Cl2, HPLC MS RT=1.81 min., MW=499.1; 1H NMR (DMSO-d6+2 drops TFA-d) δ: 2.22 (2H, m), 3.17 (4H, m), 3.26 (2H, m), 3.64 (4H, m), 4.18-4.29 (4H, m), 4.56 (2H, m), 7.22 (1H, d), 7.74 (1H, s), 7.89 (1H, m), 8.12 (1H, d), 8.81 (1H, m), 8.95 (1H, dd), 9.44 (1H, s).

Workup

extractionextracted with CH2Cl2
dry with materialOrganic layers dried with MgSO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified

Sources & evidence

ORD record: ord-c8b0e076420e4e65a894c0bc01dc0c07
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08859572B2

Reaction notes

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