Methanol → HCID 178502412, compound

HRID 1919171Notes

Reaction equation

HRID 1919171 reaction equation
CN([C:4]([O:8]N1N=NC2C=CC=NC1=2)=[N+:5](C)C)C.F[P-](F)(F)(F)(F)F.[C:25]([OH:31])([C:27]([F:30])([F:29])[F:28])=[O:26].[NH:32]1[CH2:36][CH2:35][CH2:34][C@H:33]1[C:37]1[NH:38][C:39]([C:42]2[S:43][C:44]([C:47]3[S:51][C:50]([C:52]4[NH:56][C:55]([C@@H:57]5[CH2:61][CH2:60][CH2:59][NH:58]5)=[N:54][CH:53]=4)=[N:49][CH:48]=3)=[CH:45][N:46]=2)=[CH:40][N:41]=1.[CH3:62][O:63][C:64]([NH:66][C@@H:67]([CH:71]([CH3:73])[CH3:72])[C:68]([OH:70])=O)=[O:65].CCN([CH:80]([CH3:82])[CH3:81])C(C)C.[CH3:83][OH:84]>CN(C)C=O.O>[F:28][C:27]([F:30])([F:29])[C:25]([O-:31])=[O:26].[CH3:62][O:63][C:64]([NH:66][C@@H:67]([CH:71]([CH3:73])[CH3:72])[C:68]([N:32]1[CH2:36][CH2:35][CH2:34][C@H:33]1[C:37]1[NH:41][CH:40]=[C:39]([C:42]2[S:43][C:44]([C:47]3[S:51][C:50]([C:52]4[N:56]=[C:55]([C@@H:57]5[CH2:61][CH2:60][CH2:59][N:58]5[C:25]([C@@H:27]([NH:5][C:4](=[O:8])[O:84][CH3:83])[CH:80]([CH3:81])[CH3:82])=[O:31])[NH:54][CH:53]=4)=[N:49][CH:48]=3)=[CH:45][N:46]=2)[N:38]=1)=[O:70])=[O:65]

Participants

10

Reactant 6

HCID 887MethanolHCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 53233526HCID 53233526, compound

Product 2

HCID 84468TrifluoroacetateHCID 178502412HCID 178502412, compoundYield 52%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

HATU (66 mg, 0.17 mmol) was added to a stirred solution of a TFA salt of 2,2′-bis(2-((2S)-2-pyrrolidinyl)-1H-imidazol-5-yl)-5,5′-bi-1,3-thiazole (40 mg, 0.045 mmol), (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (31 mg, 0.18 mmol) and DIEA (0.078 mL, 0.45 mmol) in dimethylformamide (2 mL) at room temperature. The reaction was stirred for 3 h, diluted with methanol (2 mL) and water (2 mL) and stirred for 15 min. The reaction mixture was concentrated to dryness in vacuo and purified by preparative HPLC (Waters Sunfire C18 column 30×150 mm 5 u, eluted with a gradient of 10 to 80% acetonitrile/water/0.1% TFA) to yield a trifluoroacetate salt of methyl ((1S)-1-(((2S)-2-(4-(2′-(2-((2S)-1-((2S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-2-pyrrolidinyl)-1H-imidazol-4-yl)-5,5′-bi-1,3-thiazol-2-yl)-1H-imidazol-2-yl)-1-pyrrolidinyl)carbonyl)-2-methylpropyl)carbamate (23 mg, 0.023 mmol, 52% yield) as a yellow solid.

Workup

  1. stirringstirred for 15 min
  2. concentrationThe reaction mixture was concentrated to dryness in vacuo
  3. custompurified by preparative HPLC (Waters Sunfire C18 column 30×150 mm 5 u
  4. washeluted with a gradient of 10 to 80% acetonitrile/water/0.1% TFA)

Sources & evidence

ORD record
ord-bd657ee2cf7046e5959b7dd76ea563f3
Source dataset
uspto-grants-2013_12
Patent number
US08618153B2

Reaction notes

Loading…