Hydrochloric Acid → HCID 178502476, compound

HRID 1751347Notes

Reaction equation

HRID 1751347 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:58]([NH:60][C@@H:61]([CH:65]1[CH2:70][CH2:69][O:68][CH2:67][CH2:66]1)[C:62]([OH:64])=O)=[O:59].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>[CH3:1][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:29]=[CH:30][C:31]([C:34]3[NH:38][C:37]([C@@H:39]5[CH2:43][CH2:42][CH2:41][N:40]5[C:62](=[O:64])[C@@H:61]([NH:60][C:58](=[O:59])[O:57][CH3:56])[CH:65]5[CH2:70][CH2:69][O:68][CH2:67][CH2:66]5)=[N:36][CH:35]=3)=[CH:32][CH:33]=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]

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 59264488(S)-2-(Methoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetic acidHCID 178502478HCID 178502478, compound

Product 1

HCID 178502476HCID 178502476, compoundYield 66.4%

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). (S)-2-(methoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetic acid (16 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 (27.6 mg). LCMS-ESI+: calc'd for C46H54N8O7: 830.97 (M+); Found: 832.56 (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-3d03c004775c4970805d54952b8a0c32
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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