1,1'-Carbonyldiimidazole → Cyclopropanecarboxylic acid, 1-amino-2-ethenyl-, ethyl ester, hydrochloride (1:1), (1R,2S)-

HRID 1852188Notes

Reaction equation

HRID 1852188 reaction equation
C(OC(N[C@@H]1C(=O)N2C[C@H](OC3C4C(=C([Cl:39])C=CC=4)C(OC)=CN=3)C[C@H]2C(=O)[NH:19][C@:18]2([C:44]([OH:46])=[O:45])[CH2:43][C@H:17]2[CH:16]=[CH:15]CCC(C)C[C@H]1C)=O)(C)(C)C.C(N1C=CN=C1)(N1[CH:55]=[CH:54]N=C1)=O.OC(C(F)(F)F)=O.FC1(S(N)(=O)=O)CC1.C1CCN2C(=NCCC2)CC1>CN(C=O)C.O>[ClH:39].[NH2:19][C@:18]1([C:44]([O:46][CH2:54][CH3:55])=[O:45])[CH2:43][C@H:17]1[CH:16]=[CH2:15]

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 86683247HCID 86683247, compoundHCID 86683249HCID 86683249, compound

Product 1

HCID 66670028Cyclopropanecarboxylic acid, 1-amino-2-ethenyl-, ethyl ester, hydrochloride (1:1), (1R,2S)-

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (2R,6S,7R,13aS,14aR,16aS,Z)-6-((tert-butoxycarbonyl)amino)-2-((5-chloro-4-methoxyisoquinolin-1-yl)oxy)-7,9-dimethyl-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylic acid (300 mg, 0.43 mmol) in DMF (20 mL) was added 1,1′-carbonyldiimidazole (CDI, 92 mg, 0.57 mmol) at room temperature. The reaction mass was heated at 50° C. for 2 h. To this hot solution was added 1-fluorocyclopropane-1-sulfonamide TFA (166 mg, 0.65 mmol) followed by DBU (135 mg, 0.87 mmol). The resulting solution was stirred at 50° C. for overnight. The reaction mass was diluted with water and extracted with ethyl acetate. The combined organic layer was washed with water, dried over anhydrous Na2SO4 and concentrated under reduced pressure to get desired product as diastereomeric mixture. The diastereomeric mixture was separated by HPLC to get desired product Compound 29 (110 mg, 33%). tert-butyl ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-2-((5-chloro-4-methoxyisoquinolin-1-yl)oxy)-14a-(((1-fluorocyclopropyl)sulfonyl)carbamoyl)-7,9-dimethyl-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-yl)carbamate MS: MS m/z 808.2 (M++1).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organic layer was washed with water
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a2b3f66c765a4706863133956a75cfcb
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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