Dimethylformamide → HCID 178502385, compound

HRID 1411369Notes

Reaction equation

HRID 1411369 reaction equation
[CH3:1][C:2]1([CH3:8])[CH2:4][C@@H:3]1[C:5](O)=[O:6].O[C:10]([C:12](F)(F)F)=[O:11].O[C:17](C(F)(F)F)=O.OC(C(F)(F)F)=O.[CH3:30][O:31][C:32](=[O:81])[NH:33][C@H:34]([C:38]([N:40]1[CH2:44][CH2:43][CH2:42][C@H:41]1[C:45]1[NH:46][CH:47]=[C:48]([C:50]2[CH:55]=[CH:54][C:53]([C:56]3[CH:61]=[CH:60][C:59]([NH:62]C(C4C=NC(N5C[C@H](C)NC[C@H]5C)=CC=4)=O)=[CH:58][C:57]=3[CH3:79])=[C:52]([CH3:80])[CH:51]=2)[N:49]=1)=[O:39])[CH:35]([CH3:37])[CH3:36].C[N:83]([CH:85]=O)C.CN(C(ON1N=[N:102][C:97]2[CH:98]=[CH:99][CH:100]=[N:101][C:96]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:111](N(CC)C(C)C)([CH3:113])[CH3:112]>>[CH3:30][O:31][C:32](=[O:81])[NH:33][C@H:34]([C:38]([N:40]1[CH2:44][CH2:43][CH2:42][C@H:41]1[C:45]1[NH:46][CH:47]=[C:48]([C:50]2[CH:55]=[CH:54][C:53]([C:56]3[CH:61]=[CH:60][C:59]([NH:62][C:10]([C:12]4[CH:85]=[N:83][C:100]([N:101]5[CH2:96][C@H:97]([CH3:17])[N:102]([C:5]([C@H:3]6[CH2:4][C:2]6([CH3:8])[CH3:1])=[O:6])[CH2:112][C@H:111]5[CH3:113])=[CH:99][CH:98]=4)=[O:11])=[CH:58][C:57]=3[CH3:79])=[C:52]([CH3:80])[CH:51]=2)[N:49]=1)=[O:39])[CH:35]([CH3:37])[CH3:36]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10192561(1S)-2,2-Dimethylcyclopropane-1-carboxylic acidHCID 178502382HCID 178502382, compound

Product 1

HCID 178502385HCID 178502385, compoundYield 98.3%

Procedure

To a mixture of (S)-(+)-2,2-dimethylcyclopropane carboxylic acid (2.39 mg, 0.021 mmol) and ((S)-1-{(S)-2-[4-(4′-{[6-((2R,5S)-2,5-dimethyl-piperazin-1-yl)-pyridine-3-carbonyl]-amino}-2,2′-dimethyl-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester tri-TFA (20 mg, 0.019 mmol, Preparation 30) in DMF (0.5 mL, 6 mmol) at RT was added HATU (7.98 mg, 0.021 mmol) followed by N,N-diisopropylethylamine (16.60 uL, 0.095 mmol). The reaction mixture was stirred at RT overnight, concentrated, dissolved in 1:1 acetic acid:water (1.5 mL), filtered, and purified by preparative HPLC to provide the di-TFA salt of the title compound (15 mg).

Workup

  1. concentrationconcentrated
  2. dissolutiondissolved in 1:1 acetic acid
  3. filtrationwater (1.5 mL), filtered
  4. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-6955b6b9af6749c5bb4cf8ba33be0786
Source dataset
uspto-grants-2014_12
Patent number
US08921372B2

Reaction notes

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