Isopropylamine → 3-(7-(isopropylcarbamoyl)-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 246409Notes

Reaction equation

HRID 246409 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][CH:26]([NH2:28])[CH3:27].[C:29]([C:32]1[C:40]2[C:35](=[N:36][CH:37]=[C:38]([C:41]3[C:49]4[CH2:48][CH2:47][CH2:46][CH2:45][C:44]=4[N:43]([CH3:50])[N+:42]=3[O-:51])[N:39]=2)[N:34]([CH2:52][O:53][CH2:54][CH2:55][Si:56]([CH3:59])([CH3:58])[CH3:57])[CH:33]=1)(O)=[O:30]>ClCCl>[CH:26]([NH:28][C:29]([C:32]1[C:40]2[C:35](=[N:36][CH:37]=[C:38]([C:41]3[C:49]4[CH2:48][CH2:47][CH2:46][CH2:45][C:44]=4[N:43]([CH3:50])[N+:42]=3[O-:51])[N:39]=2)[N:34]([CH2:52][O:53][CH2:54][CH2:55][Si:56]([CH3:59])([CH3:58])[CH3:57])[CH:33]=1)=[O:30])([CH3:27])[CH3:25]

Participants

5

Reactant 3

HCID 6363IsopropylamineHCID 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 712804953-(7-(isopropylcarbamoyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxideYield 91.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

In a 16×100 mm screw cap test tube were added HATU (46.3 mg, 122 μmol.20) and propan-2-amine (24.0 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 dichloromethane (2.50 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-(isopropylcarbamoyl)-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, 92.8 μmol, 91.5%) as a clear foam. MS (M+H)+=485.1 (100% purity); 1H NMR (CDCl3) δ: 7.91 (s, 1H), 6.41 (d, J=8.1 Hz, 1H), 6.11 (s, 1H), 4.54 (s, 2H), 3.22-3.37 (m, 1H), 2.36-2.46 (m, 2H), 2.31 (s, 3H), 1.22-1.44 (m, 2H), 1.00-1.14 (m, 2H), 0.82-1.00 (m, 4H), 0.16 (d, J=6.6 Hz, 7H), −0.30-−0.12 (m, 2H), −1.19 (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-fa40ee948bc341609068e4ad4f29594a
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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