Hydrochloric Acid → HCID 59386565, compound

HRID 2358366Notes

Reaction equation

HRID 2358366 reaction equation
[C:1]1([C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)[CH:6]=[CH:5][C:4]([C@@:7]2([O:51][CH3:52])[CH2:24][N:23]3[C@H:9]([C:10](=[O:50])[NH:11][C@:12]4([C:47](O)=[O:48])[CH2:46][C@H:13]4[CH:14]=[CH:15][CH2:16][CH2:17][CH2:18][N:19]([S:34]([C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=4[N+:43]([O-:45])=[O:44])(=[O:36])=[O:35])[CH2:20][C@H:21]([NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:22]3=[O:25])[CH2:8]2)=[CH:3][CH:2]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH:71]1([S:74]([NH2:77])(=[O:76])=[O:75])[CH2:73][CH2:72]1.C1CCN2C(=NCCC2)CC1.Cl>O1CCCC1.O>[C:1]1([C:53]2[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=2)[CH:6]=[CH:5][C:4]([C@@:7]2([O:51][CH3:52])[CH2:24][N:23]3[C@H:9]([C:10](=[O:50])[NH:11][C@:12]4([C:47](=[O:48])[NH:77][S:74]([CH:71]5[CH2:73][CH2:72]5)(=[O:76])=[O:75])[CH2:46][C@H:13]4[CH:14]=[CH:15][CH2:16][CH2:17][CH2:18][N:19]([S:34]([C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=4[N+:43]([O-:45])=[O:44])(=[O:36])=[O:35])[CH2:20][C@H:21]([NH:26][C:27](=[O:28])[O:29][C:30]([CH3:33])([CH3:31])[CH3:32])[C:22]3=[O:25])[CH2:8]2)=[CH:3][CH:2]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418CyclopropanesulfonamideHCID 59386559HCID 59386559, compound

Product 1

HCID 59386565HCID 59386565, compoundYield 54.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (2R,6S,13aS,14aR,16aS,Z)-2-(biphenyl-4-yl)-6-(tert-butoxycarbonylamino)-2-methoxy-8-(2-nitrophenylsulfonyl)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[n]pyrrolo[2,1-c][1,4,8]triazacyclopentadecine-14a-carboxylic acid (13 mg, 0.016 mmol) and CDI (3.61 mg, 0.022 mmol) in tetrahydrofuran (2 mL) was refluxed for 1 h. It was then cooled to rt and cyclopropanesulfonamide (2.70 mg, 0.022 mmol) was added followed by DBU (8.39 μL, 0.056 mmol). The reaction mixture was stirred at rt 18 h, and then it was concentrated in vacuo to yield a light yellow oil. To this oil was added 5 mL of water, adjusting to pH=4 using 1N HCl. The white precipitate was collected by filtration and washed with water to give 15 mg of the crude product as a white solid. Purification by flash chromatography eluting with 2% MeOH/CH2Cl2 gave 8 mg of tert-butyl (2R,6S,13aS,14aR,16aS,Z)-2-(biphenyl-4-yl)-14a-(cyclopropylsulfonylcarbamoyl)-2-methoxy-8-(2-nitrophenylsulfonyl)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[n]pyrrolo[2,1-c][1,4,8]triazacyclopentadecin-6-ylcarbamate as a white solid. LC-MS: MS m/z 889(M+1-MeOH). (This product was contaminated with an equal portion of the P1 methyl ester by-product.)

Workup

  1. temperaturewas refluxed for 1 h
  2. concentrationit was concentrated in vacuo
  3. customto yield a light yellow oil
  4. filtrationThe white precipitate was collected by filtration
  5. washwashed with water
  6. customto give 15 mg of the crude product as a white solid
  7. customPurification by flash chromatography
  8. washeluting with 2% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-9f11fd413eb7423db889abe4b2042074
Source dataset
uspto-grants-2010_07
Patent number
US07763584B2

Reaction notes

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