Tert-Butylamine → 3-(7-(tert-butylcarbamoyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxide

HRID 246411Notes

Reaction equation

HRID 246411 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][C:26]([NH2:29])([CH3:28])[CH3:27].[C:30]([C:33]1[C:41]2[C:36](=[N:37][CH:38]=[C:39]([C:42]3[C:50]4[CH2:49][CH2:48][CH2:47][CH2:46][C:45]=4[N:44]([CH3:51])[N+:43]=3[O-:52])[N:40]=2)[N:35]([CH2:53][O:54][CH2:55][CH2:56][Si:57]([CH3:60])([CH3:59])[CH3:58])[CH:34]=1)(O)=[O:31]>CN(C=O)C>[C:26]([NH:29][C:30]([C:33]1[C:41]2[C:36](=[N:37][CH:38]=[C:39]([C:42]3[C:50]4[CH2:49][CH2:48][CH2:47][CH2:46][C:45]=4[N:44]([CH3:51])[N+:43]=3[O-:52])[N:40]=2)[N:35]([CH2:53][O:54][CH2:55][CH2:56][Si:57]([CH3:60])([CH3:59])[CH3:58])[CH:34]=1)=[O:31])([CH3:28])([CH3:27])[CH3:25]

Participants

5

Reactant 3

HCID 6385Tert-ButylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712802803-(7-carboxy-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxide

Product 1

HCID 712800513-(7-(tert-butylcarbamoyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxideYield 85.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

In a 16×100 mm screw cap test tube were added HATU (46.3 mg, 122 μmol.20) and 2-methylpropan-2-amine (29.7 mg, 406 μmol) then 3-(7-carboxy-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxide (45 mg, 101 μmol) dissolved in DMF (2.00 mL) was added to give a light yellow solution which immediately formed a white precipitated. The reaction mixture stirred at 25° C. overnight, solvents evaporated and residue purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco) eluting with 0 to 50% EtOAc in hexanes over 30 min to yield 3-(7-(tert-butylcarbamoyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxide (43 mg, 86.2 μmol, 85.0%) as a clear foam. MS (M+H)+=499 (>90% purity); 1H NMR (CDCl3) δ: 7.82 (s, 1H), 6.21 (s, 1H), 4.52 (s, 2H), 2.36-2.45 (m, 2H), 2.30 (s, 3H), 1.23-1.37 (m, 2H), 0.95-1.12 (m, 2H), 0.89 (dd, J=10.9, 5.6 Hz, 2H), 0.72-0.85 (m, 2H), 0.37 (s, 9H), −0.29-−0.17 (m, 2H), −1.20 (s, 9H).

Workup

  1. customIn a 16×100 mm screw cap test tube
  2. additionwas added
  3. customto give a light yellow solution which
  4. customimmediately formed a white precipitated
  5. customsolvents evaporated
  6. customresidue purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco)
  7. washeluting with 0 to 50% EtOAc in hexanes over 30 min

Sources & evidence

ORD record
ord-5ea998c83e224d4db6b34944315ef660
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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