Methanamine, N-methoxy-, hydrochloride (1:1) → N-methoxy-N-methyl-4-(3-nitrophenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide

HRID 882179Notes

Reaction equation

HRID 882179 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([C:10]2[C:11]3[C:18]([C:19]([OH:21])=O)=[CH:17][N:16]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:12]=3[N:13]=[CH:14][N:15]=2)[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].Cl.[CH3:31][O:32][NH:33][CH3:34].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C)C=O>[CH3:31][O:32][N:33]([CH3:34])[C:19]([C:18]1[C:11]2[C:10]([C:6]3[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)=[N:15][CH:14]=[N:13][C:12]=2[N:16]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:27])([CH3:28])[CH3:29])[CH:17]=1)=[O:21]

Participants

6

Reactant 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 896132804-(3-nitrophenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid

Product 1

HCID 89629897N-methoxy-N-methyl-4-(3-nitrophenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To 4-(3-nitrophenyl)-7-[[2-(trimethylsilyl)ethoxy]methyl]-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid (637 mg, 1.54 mmol), methoxy(methyl)amine hydrochloride (298 mg, 3.06 mmol), was added N,N-dimethylformamide (20 mL), HATU (701 mg, 1.84 mmol) and DIPEA (793 mg, 6.14 mmol). The resulting solution was stirred for 2 hours at 25° C. and then quenched by the addition of water (50 mL). The reaction solution was extracted using ethyl acetate (×3), and the combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The product was purified by chromatography using silica gel, eluting with 50% ethyl acetate/petroleum ether. The product was collected and concentrated in vacuo to afford N-methoxy-N-methyl-4-(3-nitrophenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide as a white solid. LRMS (ESI) calc'd for C21H28N5O5Si [M+H]+: 458, found 458. 1H NMR (400 MHz, CDCl3) δ 9.07 (s, 1H), 8.59 (s, 1H), 8.36 (d, J=8.4 Hz, 1H), 8.18 (d, 8.4 Hz, 1H), 7.95 (s, 1H), 7.70 (t, J=7.8 Hz, 1H), 5.78 (s, 2H), 3.64 (t, J=8.2 Hz, 2H), 3.49 (s, 3H), 3.09 (s, 3H), 0.98 (t, J=8.2 Hz, 2H), 0.04 (s, 9H).

Workup

  1. customquenched by the addition of water (50 mL)
  2. extractionThe reaction solution was extracted
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe product was purified by chromatography
  8. washeluting with 50% ethyl acetate/petroleum ether
  9. customThe product was collected
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-08d425b1035c4ee9948a24b1652c79d4
Source dataset
uspto-grants-2015_03
Patent number
US08993756B2

Reaction notes

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