Dimethylacetamide → HCID 67495830, compound

HRID 1776051Notes

Reaction equation

HRID 1776051 reaction equation
Cl.Cl.Cl.[CH3:4][O:5][C:6](=[O:53])[NH:7][C@H:8]([C:12]([N:14]1[CH2:18][CH2:17][CH2:16][C@H:15]1[C:19]1[NH:20][C:21]([C:24]2[CH:29]=[CH:28][C:27]([C:30]3[CH:35]=[CH:34][C:33]([NH:36][C:37]([C:39]4[CH:40]=[N:41][C:42]([N:45]5[CH2:50][CH2:49][NH:48][CH2:47][C@H:46]5[CH3:51])=[CH:43][CH:44]=4)=[O:38])=[CH:32][C:31]=3[CH3:52])=[CH:26][CH:25]=2)=[CH:22][N:23]=1)=[O:13])[CH:9]([CH3:11])[CH3:10].C(N(CC)C(C)C)(C)C.CC(N(C)C)=O.[C:69]([N:72]1[CH2:76][CH2:75][CH2:74][C@@:73]1([CH3:80])[C:77](O)=[O:78])(=[O:71])[CH3:70].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>>[CH3:4][O:5][C:6](=[O:53])[NH:7][C@H:8]([C:12]([N:14]1[CH2:18][CH2:17][CH2:16][C@H:15]1[C:19]1[NH:20][C:21]([C:24]2[CH:25]=[CH:26][C:27]([C:30]3[CH:35]=[CH:34][C:33]([NH:36][C:37]([C:39]4[CH:40]=[N:41][C:42]([N:45]5[CH2:50][CH2:49][N:48]([C:77]([C@:73]6([CH3:80])[CH2:74][CH2:75][CH2:76][N:72]6[C:69](=[O:71])[CH3:70])=[O:78])[CH2:47][C@H:46]5[CH3:51])=[CH:43][CH:44]=4)=[O:38])=[CH:32][C:31]=3[CH3:52])=[CH:28][CH:29]=2)=[CH:22][N:23]=1)=[O:13])[CH:9]([CH3:11])[CH3:10]

Participants

6

Reactant 5

HCID 31374DimethylacetamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67495230HCID 67495230, compoundHCID 131734756((S)-2-methyl-1-{(S)-2-[5-(2'-methyl-4'-{[6-((R)-2-methyl-piperazin-1-yl)-pyridine-3-carbonyl]-amino}-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-propyl)-carbamic acid methyl ester tri-HCl

Product 1

HCID 67495830HCID 67495830, compoundYield 57.6%

Procedure

To a solution of [(((S)-2-methyl-1-{(S)-2-[5-(2′-methyl-4′-{[6-((R)-2-methyl-piperazin-1-yl)-pyridine-3-carbonyl]-amino}-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-propyl)-carbamic acid methyl ester tri-HCl (15 mg, 0.019 mmol; Preparation 18) and N,N-diisopropylethylamine (33.1 uL, 0.190 mmol) dissolved in DMA (0.6 mL, 7 mmol) was added (S)-1-acetyl-2-methyl-pyrrolidine-2-carboxylic acid (3.2 mg, 0.019 mmol, Preparation 19) and HATU (11 mg, 0.028 mmol). The reaction mixture was stirred at room temperature overnight, concentrated, dissolved in 1:1 acetic acid:water (4 mL) and purified by preparative HPLC to provide the di-TFA salt of the title compound (9.1 mg). (m/z): [M+H]+ calcd for C46H57N9O6 832.44 found 832.4.

Workup

  1. concentrationconcentrated
  2. dissolutiondissolved in 1:1 acetic acid
  3. customwater (4 mL) and purified by preparative HPLC

Sources & evidence

ORD record
ord-f61a12a8bf3d4db9a4c205c51a439995
Source dataset
uspto-grants-2016_02
Patent number
US09260414B2

Reaction notes

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