Sodium hydride → 5-Bromo-1-(2-trimethylsilanyl-ethoxymethyl)-3-(1-trityl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine

HRID 1924468Notes

Reaction equation

HRID 1924468 reaction equation
C1(S([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([Br:19])[CH:18]=[C:13]3[C:12]([C:20]3[CH:21]=[N:22][N:23]([C:25]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH:24]=3)=[CH:11]2)(=O)=O)C=CC=CC=1.[H-].[Na+].[CH3:46][Si:47]([CH2:50][CH2:51][O:52][CH2:53]Cl)([CH3:49])[CH3:48].[NH4+].[Cl-]>CN(C=O)C.CCOC(C)=O>[Br:19][C:17]1[CH:18]=[C:13]2[C:12]([C:20]3[CH:21]=[N:22][N:23]([C:25]([C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)[C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH:24]=3)=[CH:11][N:10]([CH2:53][O:52][CH2:51][CH2:50][Si:47]([CH3:49])([CH3:48])[CH3:46])[C:14]2=[N:15][CH:16]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 104167581-Benzenesulfonyl-5-bromo-3-(1-trityl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 591286885-Bromo-1-(2-trimethylsilanyl-ethoxymethyl)-3-(1-trityl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridineYield 55%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of azaindole 1 (0.5 g, 0.99 mmol) in DMF (2.5 mL) was added NaH (60% w/w in mineral oil, 59.4 mg, 1.48 mmol) portionwise. Then the reaction mixture was stirred for 0.5 h. SEM-Cl (263 μL, 1.48 mmol) was then added in one portion. The reaction mixture was stirred overnight and poured cautiously onto a stirred mixture of EtOAc (20 mL)/saturated aq. NH4Cl (20 mL). The layers were separated. The aqueous layer was extracted with EtOAc (2×30 mL), the combined organic extracts dried (MgSO4) and concentrated. The residue was purified by SGC using EtOAc:hexane (gradient elution up to 8:92, v/v) to give (III-d) as a white foam (345 mg, 55%); 1H NMR (400 MHz, CDCl3) δ 0.002 (9H, s), 0.97 (t, J=8.3 Hz, 2H), 3.58 (t, J=8.3 Hz, 2H), 5.69 (s, 2H), 7.30 (m, 6H), 7.40 (m, 9H), 7.46 (s, 1H), 7.65 (s, 1H), 7.98 (d, J=0.7 Hz, 1H), 8.06 (d, J=2.1 Hz, 1H), 8.41 (d, J=2.2 Hz, 1H).

Workup

  1. stirringThe reaction mixture was stirred overnight
  2. customThe layers were separated
  3. extractionThe aqueous layer was extracted with EtOAc (2×30 mL)
  4. dry with materialthe combined organic extracts dried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was purified by SGC
  7. washhexane (gradient elution up to 8:92

Sources & evidence

ORD record
ord-89668e8718a3471e806c9599784f2523
Source dataset
uspto-grants-2012_05
Patent number
US08178552B2

Reaction notes

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