Isopropyl isocyanate → (3aR,7S,10S,12R,21E,24aS)-7-cyclopentyl-10-({(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}carbamoyl)-5,8-dioxo-1,2,3,3a,5,6,7,8,11,12,20,23,24,24a-tetradecahydro-10H-9,12-methanocyclopenta[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinolin-19-yl propan-2-ylcarbamate

HRID 522390Notes

Reaction equation

HRID 522390 reaction equation
[CH:1]1([C@H:6]2[C:33](=[O:34])[N:32]3[CH2:35][C@@H:29]([CH2:30][C@H:31]3[C:36]([NH:38][C@:39]3([C:44](=[O:52])[NH:45][S:46]([CH:49]4[CH2:51][CH2:50]4)(=[O:48])=[O:47])[CH2:41][C@H:40]3[CH:42]=[CH2:43])=[O:37])[O:28][C:18]3=[N:19][C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=4[C:26]([OH:27])=[C:17]3[CH2:16][CH:15]=[CH:14][CH2:13][CH2:12][C@@H:11]3[CH2:53][CH2:54][CH2:55][C@H:10]3[O:9][C:8](=[O:56])[NH:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:57]([N:60]=[C:61]=[O:62])([CH3:59])[CH3:58]>ClC(Cl)C.CN(C1C=CN=CC=1)C.C(OCC)(=O)C.O>[CH3:58][CH:57]([NH:60][C:61](=[O:62])[O:27][C:26]1[C:25]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[N:19]=[C:18]2[O:28][C@H:29]3[CH2:35][N:32]([C:33](=[O:34])[C@H:6]([CH:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)[NH:7][C:8](=[O:56])[O:9][C@@H:10]4[CH2:55][CH2:54][CH2:53][C@H:11]4[CH2:12][CH2:13][CH:14]=[CH:15][CH2:16][C:17]=12)[C@H:31]([C:36](=[O:37])[NH:38][C@:39]1([C:44](=[O:52])[NH:45][S:46]([CH:49]2[CH2:50][CH2:51]2)(=[O:47])=[O:48])[CH2:41][C@H:40]1[CH:42]=[CH2:43])[CH2:30]3)[CH3:59]

Participants

7

Reactant 2

HCID 61277Isopropyl isocyanateHCID 178455696HCID 178455696, compound

Product 1

HCID 117599051(3aR,7S,10S,12R,21E,24aS)-7-cyclopentyl-10-({(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}carbamoyl)-5,8-dioxo-1,2,3,3a,5,6,7,8,11,12,20,23,24,24a-tetradecahydro-10H-9,12-methanocyclopenta[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinolin-19-yl propan-2-ylcarbamate

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 63651,1-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (3aR,7S,10S,12R,21E,24aS)-7-cyclopentyl-N-{(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}-19-hydroxy-5,8-dioxo-1,2,3,3a,5,6,7,8,11,12,20,23,24,24a-tetradecahydro-10H-9,12-methanocyclopenta[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinoline-10-carboxamide (Example 17) (30 mg) in dichloroethane (0.6 mL) was added isopropylisocyanate (0.037 mL) then DMAP (4.6 mg). The reaction mixture was heated to 50° C. for 1 hour. After cooling back to room temperature, the mixture was diluted with ethyl acetate and water was added. The mixture was extracted with ethyl acetate (3×). The combined organics were dried over magnesium sulfate, filtered and concentrated. Purification by reverse phase HPLC (40% ACN-100% ACN/0.05% TFA/water) yielded 27 mg of the desired product after workup with NaHCO3 and ethyl acetate. HRMS (ES+) m/z 875.3981 (M+H)+.

Workup

  1. temperatureAfter cooling back to room temperature
  2. additionwas added
  3. extractionThe mixture was extracted with ethyl acetate (3×)
  4. dry with materialThe combined organics were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by reverse phase HPLC (40% ACN-100% ACN/0.05% TFA/water)

Sources & evidence

ORD record
ord-19a70518a53e4b93905a2012f7156c04
Source dataset
uspto-grants-2016_05
Patent number
US09328138B2

Reaction notes

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