Methanol → HCID 178502411, compound

HRID 1919172Notes

Reaction equation

HRID 1919172 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 28377962N-(Methoxycarbonyl)-D-valineHCID 53233526HCID 53233526, compound

Product 2

HCID 84468TrifluoroacetateHCID 178502411HCID 178502411, compoundYield 36%

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), (R)-2-(methoxycarbonylamino)-3-methylbutanoic acid (31.3 mg, 0.179 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 ((1R)-1-(((2S)-2-(4-(2′-(2-((2S)-1-((2R)-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 (16 mg, 0.016 mmol, 36% yield) as an orange 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-02bafb16bc6c46a1a639323ee2fd164c
Source dataset
uspto-grants-2013_12
Patent number
US08618153B2

Reaction notes

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