Hydrochloric Acid → HCID 67102919, compound

HRID 2081128Notes

Reaction equation

HRID 2081128 reaction equation
Cl.[Cl:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH2:5][N:6]([C:12]([O:14][C@@H:15]1[CH2:19][C@@H:18]([C:20](=[O:36])[NH:21][C@:22]3([C:27](=[O:35])[NH:28][S:29]([CH:32]4[CH2:34][CH2:33]4)(=[O:31])=[O:30])[CH2:24][C@H:23]3[CH:25]=[CH2:26])[NH:17][CH2:16]1)=[O:13])[CH2:7]2.[C:37]([O:41][C:42]([C@@H:44]([CH:48]1[CH2:53][CH2:52][CH2:51][CH2:50][CH2:49]1)[C:45](O)=[O:46])=[O:43])([CH3:40])([CH3:39])[CH3:38].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl>CN(C=O)C.O>[CH:32]1([S:29]([NH:28][C:27]([C@@:22]2([NH:21][C:20]([C@H:18]3[N:17]([C:45](=[O:46])[C@@H:44]([C:42]([O:41][C:37]([CH3:39])([CH3:38])[CH3:40])=[O:43])[CH:48]4[CH2:53][CH2:52][CH2:51][CH2:50][CH2:49]4)[CH2:16][C@H:15]([O:14][C:12]([N:6]4[CH2:5][C:4]5[C:8](=[CH:9][CH:10]=[CH:11][C:3]=5[Cl:2])[CH2:7]4)=[O:13])[CH2:19]3)=[O:36])[CH2:24][C@H:23]2[CH:25]=[CH2:26])=[O:35])(=[O:31])=[O:30])[CH2:33][CH2:34]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57463498HCID 57463498, compoundHCID 57463500HCID 57463500, compound

Product 1

HCID 67102919HCID 67102919, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A 25 mL round-bottomed flask was charged with (3R,5S)-5-(((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-3-yl 4-chloroisoindoline-2-carboxylate hydrochloride (0.500 g, 0.894 mmol), (S)-2-(tert-butoxycarbonyl)-2-cyclohexylacetic acid (276 mg, 1.07 mmol) and HATU (408 mg, 1.07 mmol) in dry DMF (9 mL). The solution was cooled on an ice-water bath and treated with DIEA (0.467 mL, 2.68 mmol) by dropwise addition. The mixture was stirred at 0° C. for 1 h, then allowed to warm up and stirred at room temperature for 16 h. The mixture was diluted with water (50 mL) and the pH adjusted to 3 with 1N HCl, the mixture was extracted with Et2O (3×20 mL). The combined organic extracts were then washed with 1N HCl (3×20 mL), water (3×20 mL) and brine (3×20 mL). The organic extract was then dried over MgSO4, filtered and concentrated. The crude material was the purified by chromatography (Biotage) eluting with 1-3% MeOH—CH2Cl2 to give the product as a white foam, (394 mg, 59%). MS m/e 662 (M+−Boc).

Workup

  1. temperatureThe solution was cooled on an ice-water bath
  2. temperatureto warm up
  3. stirringstirred at room temperature for 16 h
  4. extractionthe mixture was extracted with Et2O (3×20 mL)
  5. washThe combined organic extracts were then washed with 1N HCl (3×20 mL), water (3×20 mL) and brine (3×20 mL)
  6. extractionThe organic extract
  7. dry with materialwas then dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by chromatography (Biotage)
  11. washeluting with 1-3% MeOH—CH2Cl2

Sources & evidence

ORD record
ord-1c4541d170b34cd29525b71d93024321
Source dataset
uspto-grants-2011_04
Patent number
US07932277B2

Reaction notes

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