Serinol → HCID 71280553, compound

HRID 246459Notes

Reaction equation

HRID 246459 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:17]=[C:16]4[C:18]([C:29](O)=[O:30])=[CH:19][N:20]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:15]4=[N:14][CH:13]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[NH2:65][CH:66]([CH2:69][OH:70])[CH2:67][OH:68]>CN(C=O)C.C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:17]=[C:16]4[C:18]([C:29]([NH:65][CH:66]([CH2:69][OH:70])[CH2:67][OH:68])=[O:30])=[CH:19][N:20]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:26])([CH3:27])[CH3:28])[C:15]4=[N:14][CH:13]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 68294SerinolHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712796712-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 71280553HCID 71280553, compoundYield 46.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred mixture of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid (0.07 g, 0.15 mmol) and HATU (0.07 g, 0.18 mmol) in DMF (4.0 mL) was added N,N-diisopropyl-ethylamine (0.024 g, 0.032 mL, 0.18 mmol). The mixture was stirred at room temperature for 30 minutes then 2-aminopropane-1,3-diol (0.021 g, 0.23 mmol) was added. After 18 h the reaction mixture was diluted with ethyl acetate and water. The aqueous phase was extracted with EtOAc then the combined organic phase was washed with water and brine, dried (MgSO4), filtered and concentrated. The residue was collected by filtration, washed with dichloromethane and dried in vacuum oven to give 2-(6-chloro-1-methyl-1H-indazol-3-yl)-N-(1,3-dihydroxypropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (0.035 g, 0.07 mmol, 43%) as a white solid. 1H NMR (CDCl3) δ: 9.24 (s, 1H), 8.75 (d, J=7.3 Hz, 1H), 8.57 (d, J=8.5 Hz, 1H), 8.35 (s, 1H), 7.44 (s, 1H), 7.24 (s, 1H), 5.68 (s, 2H), 4.42 (br. s., 1H), 4.14 (s, 3H), 4.01-4.12 (m, 4H), 3.57 (t, J=8.0 Hz, 2H), 2.51 (br. s., 2H), 0.94 (t, J=7.9 Hz, 2H), −0.04 (s, 9H)

Workup

  1. extractionThe aqueous phase was extracted with EtOAc
  2. washthe combined organic phase was washed with water and brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. filtrationThe residue was collected by filtration
  7. washwashed with dichloromethane
  8. customdried in vacuum oven

Sources & evidence

ORD record
ord-3835e9aba9b048cfaa1368249e99d812
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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