Hydrochloric Acid → HCID 178502477, compound

HRID 1751346Notes

Reaction equation

HRID 1751346 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:52]([CH3:54])[CH3:53])[C:7]([N:9]1[C@H:14]([C:15]2[NH:19][C:18]3[C:20]4[C:25]([CH:26]=[CH:27][C:17]=3[N:16]=2)=[CH:24][C:23]([C:28]2[CH:33]=[CH:32][C:31]([C:34]3[NH:38][C:37]([C@@H:39]5[CH2:43][CH2:42][CH2:41][N:40]5C(OC(C)(C)C)=O)=[N:36][CH:35]=3)=[CH:30][CH:29]=2)=[CH:22][CH:21]=4)[C@@H:13]2[CH2:51][C@H:10]1[CH2:11][CH2:12]2)=[O:8])=[O:4].Cl.[CH3:56][O:57][C@H:58]([CH3:68])[C@H:59]([NH:63][C:64]([O:66][CH3:67])=[O:65])[C:60]([OH:62])=O.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>C(Cl)Cl.CO.CN(C=O)C>[CH3:56][O:57][C@H:58]([CH3:68])[C@H:59]([NH:63][C:64](=[O:65])[O:66][CH3:67])[C:60]([N:40]1[CH2:41][CH2:42][CH2:43][C@H:39]1[C:37]1[NH:38][C:34]([C:31]2[CH:32]=[CH:33][C:28]([C:23]3[CH:24]=[C:25]4[C:20](=[CH:21][CH:22]=3)[C:18]3[NH:19][C:15]([C@@H:14]5[C@@H:13]6[CH2:51][C@@H:10]([CH2:11][CH2:12]6)[N:9]5[C:7](=[O:8])[C@@H:6]([NH:5][C:3]([O:2][CH3:1])=[O:4])[CH:52]([CH3:53])[CH3:54])=[N:16][C:17]=3[CH:27]=[CH:26]4)=[CH:29][CH:30]=2)=[CH:35][N:36]=1)=[O:62]

Participants

9

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 59540170(2S,3R)-3-methoxy-2-(methoxycarbonylamino)butanoic acidHCID 178502478HCID 178502478, compound

Product 1

HCID 178502477HCID 178502477, compoundYield 57.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
35 °C

Procedure

(S)-tert-butyl 2-(5-(4-(2-((1R,3S,4S)-2-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-2-azabicyclo[2.2.1]heptan-3-yl)-1H-naphtho[1,2-d]imidazol-7-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (73 mg, 0.10 mmol) in DCM (3 mL) and MeOH (3 mL) was added HCl (4M in dioxane, 0.5 mL). The solution stirred for 3 h at 35° C., after which the solvent was removed. The intermediate (31 mg, 0.13 mmol) was dissolved in DMF (1 mL). (2S,3R)-3-methoxy-2-(methoxycarbonylamino)butanoic acid (9 mg, 0.05 mmol), HATU (19 mg, 0.05 mmol), and DIPEA (0.04 mL, 0.25 mmol) were added sequentially. The solution stirred o/n and the mixture was purified by HPLC to yield product (23.1 mg). LCMS-ESI+: calc'd for C44H52N8O7: 804.93 (M+); Found: 806.34 (M+H+).

Workup

  1. customafter which the solvent was removed
  2. stirringThe solution stirred o/n and the mixture
  3. customwas purified by HPLC

Sources & evidence

ORD record
ord-c1f9be2989a94f868197efb58f515b1c
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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