Hydrochloric Acid → HCID 59236985, compound

HRID 2407589Notes

Reaction equation

HRID 2407589 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[N:26]([CH2:29][C:30]([C:32]1[CH:33]=[CH:34][C:35]2[N:39]=[C:38]([C@@H:40]3[CH2:44][CH2:43][CH2:42][NH:41]3)[NH:37][C:36]=2[CH:45]=1)=[O:31])=[N+:27]=[N-:28].Cl.[CH3:47][N:48]([CH3:59])[C@H:49]([C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)[C:50](O)=[O:51].CCN(C(C)C)C(C)C>CN(C)C=O>[N:26]([CH2:29][C:30]([C:32]1[CH:33]=[CH:34][C:35]2[N:39]=[C:38]([C@@H:40]3[CH2:44][CH2:43][CH2:42][N:41]3[C:50](=[O:51])[C@H:49]([N:48]([CH3:47])[CH3:59])[C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=3)[NH:37][C:36]=2[CH:45]=1)=[O:31])=[N+:27]=[N-:28]

Participants

7

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 45835119(R)-a-(Dimethylamino)benzeneacetic acid HClHCID 86639969HCID 86639969, compound

Product 1

HCID 59236985HCID 59236985, compoundYield 50.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of J.31 (1.8 g, 4.86 mmol) in ethyl acetate (5 mL) was added HCl/dioxane (10 mL of 4N), and the reaction was stirred 4 hr. The solvents were removed in vacuo, and the HCl salt was exposed to high vacuum for 18 h to give (S)-2-azido-1-(2-(pyrrolidin-2-yl)-1H-benzo[d]imidazol-6-yl)ethanone.2HCl a yellow solid. HATU (1.94 g, 5.10 mmol) was added to the HCl salt of (S)-2-azido-1-(2-(pyrrolidin-2-yl)-1H-benzo[d]imidazol-6-yl)ethanone (1.8 g, 4.86 mmol), (R)-2-(dimethylamino)-2-phenylacetic acid HCl salt (1.05 g, 4.86 mmol), and Hunig's base (3.4 mL, 19.4 mmol) in dimethylformamide (50 mL) while being rapidly stirred 6 h. The solvent was removed in vacuo and the reside was partitioned into two lots and separately pre-absorbed onto SiO2 (dichloromethane), and subjected to flash chromatography on a 40 M Biotage silica gel column pre-equilibrated 2% B, and eluted with 2% B (150 mL); Segment 2: 2-40% B (1200 mL); Segment 3: 40-80% (600 mL). A=dichloromethane; B=25% methanol/dichloromethane to give J.31a (R)-1-((S)-2-(6-(2-azidoacetyl)-1H-benzo[d]imidazol-2-yl)pyrrolidin-1-yl)-2-(dimethylamino)-2-phenylethanone (combined lots: 1.05 g (50%)) as a yellow foam. 1H NMR (500 MHz, DMSO-d6) δ: 8.16 (s, 1H), 7.82 (dd, J=8.8, 1.5 Hz, 1H), 7.65 (d, J=8.5 Hz, 1H), 7.60-7.56 (m, 5H), 5.51 (s, 1H), 5.22 (dd, J=8.2, 2.8, 1H), 4.95 (m, 2H), 4.09-4.05 (m, 1H), 3.17-3.12 (m, 1H), 2.90/2.84 (br. s, 6H), 2.23-2.19 (m, 1H), 2.21-1.89 (m, 3H). LC (D-Cond. 1): RT=1.5 min; LC/MS: Anal. Calcd. for [M+H]+ C23H26N7O2: 432.22; found: 431.93. HRMS: Anal. Calcd. for [M+H]+ C23H26N7O2: 432.2148; found: 432.2127.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe reside was partitioned into two lots
  3. customseparately pre-absorbed onto SiO2 (dichloromethane)
  4. washeluted with 2% B (150 mL)

Sources & evidence

ORD record
ord-7929304c65f342b296bf5dab969c668c
Source dataset
uspto-grants-2014_08
Patent number
US08809548B2

Reaction notes

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