Pyrrolidine → HCID 117599154, compound

HRID 522387Notes

Reaction equation

HRID 522387 reaction equation
[CH:1]1([C@H:6]2[C:37](=[O:38])[N:36]3[CH2:39][C@@H:33]([CH2:34][C@H:35]3[C:40](=[O:56])[NH:41][C@:42]3([C:47](=[O:55])[NH:48][S:49]([CH:52]4[CH2:54][CH2:53]4)(=[O:51])=[O:50])[CH2:44][C@H:43]3[CH:45]=[CH2:46])[O:32][C:18]3=[N:19][C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=4[C:26]([O:27][CH2:28][C:29](O)=[O:30])=[C:17]3[CH2:16][CH:15]=[CH:14][CH2:13][CH2:12][C@@H:11]3[CH2:57][CH2:58][CH2:59][C@H:10]3[O:9][C:8](=[O:60])[NH:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:61]1[CH2:65][CH2:64][CH2:63][CH2:62]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH:1]1([C@H:6]2[C:37](=[O:38])[N:36]3[CH2:39][C@@H:33]([CH2:34][C@H:35]3[C:40]([NH:41][C@:42]3([C:47](=[O:55])[NH:48][S:49]([CH:52]4[CH2:54][CH2:53]4)(=[O:50])=[O:51])[CH2:44][C@H:43]3[CH:45]=[CH2:46])=[O:56])[O:32][C:18]3=[N:19][C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=4[C:26]([O:27][CH2:28][C:29](=[O:30])[N:61]4[CH2:65][CH2:64][CH2:63][CH2:62]4)=[C:17]3[CH2:16][CH:15]=[CH:14][CH2:13][CH2:12][C@@H:11]3[CH2:57][CH2:58][CH2:59][C@H:10]3[O:9][C:8](=[O:60])[NH:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 117599109HCID 117599109, compound

Product 1

HCID 117599154HCID 117599154, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of {[(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]oxy}acetic acid (Example 66) (27 mg) in DMF (0.5 mL) was added pyrrolidine (5.27 μL), DIPEA (0.028 mL) and HATU (14.53 mg). The reaction mixture was stirred at room temperature for 15 minutes. The reaction was quenched with water and 5% KHSO4 until pH=3. More water was added and the mixture was stirred 5 minutes. The white solid was filtered (washed with water). This solid was dissolved in ethyl acetate and the mixture was dried over magnesium sulfate, filtered and concentrated to afford the desired product (26 mg). HRMS (ES+) m/z 901.4109 (M+H)+.

Workup

  1. customThe reaction was quenched with water and 5% KHSO4 until pH=3
  2. additionMore water was added
  3. stirringthe mixture was stirred 5 minutes
  4. filtrationThe white solid was filtered
  5. wash(washed with water)
  6. dissolutionThis solid was dissolved in ethyl acetate
  7. dry with materialthe mixture was dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-829b1be5920a483aaebf4031cc562b35
Source dataset
uspto-grants-2016_05
Patent number
US09328138B2

Reaction notes

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