1,1'-Carbonyldiimidazole → HCID 68790756, compound

HRID 1171948Notes

Reaction equation

HRID 1171948 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:23](=[O:24])[N:22]2[CH2:25][C@H:26]([O:28][C:29]([N:31]3[CH2:39][C:38]4[C:33](=[CH:34][CH:35]=[CH:36][C:37]=4[F:40])[CH2:32]3)=[O:30])[CH2:27][C@H:21]2[C:20](=[O:41])[NH:19][C@:18]2([C:43]([OH:45])=O)[CH2:42][C@H:17]2[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12][O:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1(C(N2C=CN=C2)=O)C=CN=C1.[CH:58]1([S:61]([NH2:64])(=[O:63])=[O:62])[CH2:60][CH2:59]1.C1CCN2C(=NCCC2)CC1.S([O-])(O)(=O)=O.[K+]>C1(C)C=CC=CC=1.O>[F:40][C:37]1[CH:36]=[CH:35][CH:34]=[C:33]2[C:38]=1[CH2:39][N:31]([C:29]([O:28][C@H:26]1[CH2:25][N:22]3[C:23](=[O:24])[C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:10][O:11][CH2:12][CH2:13][CH2:14][CH:15]=[CH:16][C@@H:17]4[CH2:42][C@@:18]4([C:43](=[O:45])[NH:64][S:61]([CH:58]4[CH2:60][CH2:59]4)(=[O:63])=[O:62])[NH:19][C:20](=[O:41])[C@@H:21]3[CH2:27]1)=[O:30])[CH2:32]2

Participants

8

Reactant 5

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 516920Potassium bisulfateHCID 15765418CyclopropanesulfonamideHCID 68789384HCID 68789384, compound

Product 1

HCID 68790756HCID 68790756, compoundYield 96.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

(2R,6S,13aS,14aR,16aS,Z)-6-(tert-butoxycarbonylamino)-2-(4-fluoroisoindoline-2-carbonyloxy)-5,16-dioxo-2,3,5,6,7,9,10,11,13a,14,14a,15,16,16a-tetradecahydro-1H-cyclopropa(i)pyrrolo[1,2-e][1,5,8]oxadiazacyclopentadecine-14a-carboxylic acid (0.085 g, 0.13 mmol) in toluene (3 mL) was added di(1H-imidazol-1-yl)methanone (0.028 g, 0.18 mmol) in rt. The reaction was stirred at 60° C. for 3 hrs. Cyclopropanesulfonamide (0.029 g, 0.24 mmol) was added, followed by addition of DBU (0.036 ml, 0.24 mmol). The reaction was then stirred at rt for 17 hrs. Water (5 mL) was added and acidified with saturated potassium hydrogen sulfate until pH=2˜3. The mixture was extracted with ethyl acetate (20 mL), washed with brine and dried over sodium sulfate. After removal of solvent, the residue was purified by chromatography (Hexane:Ethyl acetate=1:3) to give (2R,6S,13aS,14aR,16aS,Z)-6-(tert-butoxycarbonylamino)-14a-(cyclopropylsulfonylcarbamoyl)-5,16-dioxo-2,3,5,6,7,9,10,11,13a,14,14a,15,16,16a-tetradecahydro-1H-cyclopropa(i)pyrrolo[1,2-e][1,5,8]oxadiazacyclopentadecin-2-yl 4-fluoroisoindoline-2-carboxylate as white solid (0.092 g, 93%). MS: Calcd.: 733; Found: [M+H]+ 734. 1H NMR (400 MHz, d6-DMSO) δ11.20 (s, 1H), 8.28 (m, 1H), 7.35 (m, 1H), 7.12-7.20 (m, 2H), 7.00 (m, 1H), 5.57 (m, 1H), 5.35 (m, 1H), 5.16 (m, 1H), 4.67 (s, 4H), 4.41 (m, 2H), 4.15 (m, 1H), 3.86 (m, 1H), 3.62 (m, 1H), 3.45 (m, 1H), 3.31 (m, 1H), 2.91 (m, 1H), 2.33 (m, 4H), 1.68 (m, 2H), 1.49 (m, 3H), 1.11-1.26 (m, 14H).

Workup

  1. stirringThe reaction was then stirred at rt for 17 hrs
  2. extractionThe mixture was extracted with ethyl acetate (20 mL)
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. customAfter removal of solvent
  6. customthe residue was purified by chromatography (Hexane:Ethyl acetate=1:3)

Sources & evidence

ORD record
ord-c17acb5202d74566a6f4500d98c47ff3
Source dataset
uspto-grants-2010_11
Patent number
US07829665B2

Reaction notes

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