1,1'-Carbonyldiimidazole → HCID 90096263, compound

HRID 927286Notes

Reaction equation

HRID 927286 reaction equation
C1N=CN(C(N2C=NC=C2)=O)C=1.[F:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[C:29]([CH2:30][CH2:31][CH2:32][CH2:33][C:34](O)=[O:35])=[CH:28][C:27]3[C:22](=[CH:23][CH:24]=[C:25]([C:37](=[O:48])[NH:38][C@@H:39]([C:41]4[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=4)[CH3:40])[CH:26]=3)[C:21]2=[O:49])=[CH:16][CH:15]=1.C1CCN2C(=NCCC2)CC1.[CH:61]1([S:64]([NH2:67])(=[O:66])=[O:65])[CH2:63][CH2:62]1>O1CCCC1>[CH:61]1([S:64]([NH:67][C:34](=[O:35])[CH2:33][CH2:32][CH2:31][CH2:30][C:29]2[N:20]([C:17]3[CH:18]=[CH:19][C:14]([F:13])=[CH:15][CH:16]=3)[C:21](=[O:49])[C:22]3[C:27]([CH:28]=2)=[CH:26][C:25]([C:37]([NH:38][C@@H:39]([C:41]2[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=2)[CH3:40])=[O:48])=[CH:24][CH:23]=3)(=[O:66])=[O:65])[CH2:63][CH2:62]1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418CyclopropanesulfonamideHCID 90094257HCID 90094257, compound

Product 1

HCID 90096263HCID 90096263, compoundYield 47.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

CDI (13.50 mg, 0.083 mmol) was added to a stirred, room temperature mixture of (R)-5-(2-(4-fluorophenyl)-6-((1-(4-fluorophenyl)ethyl)carbamoyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoic acid (28 mg, 0.055 mmol) in tetrahydrofuran (2 mL) and the mixture was stirred at 70° C. for 2 h. DBU (0.017 mL, 0.111 mmol) and cyclopropylsulfonamide (10.09 mg, 0.083 mmol) were added, the resultant mixture was kept stirring at room temperature overnight. The mixture was concentrated, and the residue was purified via PTLC (Emerck 1 mm), eluted with CH2Cl2/MeOH=10:1 to give (R)-3-(5-(cyclopropanesulfonamido)-5-oxopentyl)-2-(4-fluorophenyl)-N-(1-(4-fluorophenyl)ethyl)-1-oxo-1,2-dihydroisoquinoline-6-carboxamide (16 mg) as a white solid. LCMS [M+H]+=608. 1H NMR (500 MHz, DMSO) δ ppm: 9.06 (d, J=7.88 Hz, 1H), 8.20 (d, J=8.20 Hz, 1H), 8.15 (s, 1H), 7.36-7.50 (m, 6H), 7.18 (t, J=8.99 Hz, 2H), 6.69 (s, 1H), 5.22 (t, J=7.25 Hz, 1H), 3.16-3.19 (m, 1H), 2.87-2.94 (m, 1H), 2.26 (br. s, 2H), 2.16 (br. s, 2H), 1.51 (d, J=7.25 Hz, 3H), 1.43 (br. s, 3H), 0.98-1.05 (m, 4H).

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was purified via PTLC (Emerck 1 mm)
  3. washeluted with CH2Cl2/MeOH=10:1

Sources & evidence

ORD record
ord-c12b51f9bc0b43cdbefdf146628670c2
Source dataset
uspto-grants-2016_03
Patent number
US09290454B2

Reaction notes

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