Dichloromethane → 3-(3-bromophenyl)-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanal

HRID 45029Notes

Reaction equation

HRID 45029 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.[Br:11][C:12]1[CH:13]=[C:14]([CH:18]([N:25]2[CH:29]=[C:28]([C:30]3[C:31]4[CH:38]=[CH:37][N:36]([CH2:39][O:40][CH2:41][CH2:42][Si:43]([CH3:46])([CH3:45])[CH3:44])[C:32]=4[N:33]=[CH:34][N:35]=3)[CH:27]=[N:26]2)[CH2:19][C:20](OCC)=[O:21])[CH:15]=[CH:16][CH:17]=1.C(Cl)Cl>CCCCCC>[Br:11][C:12]1[CH:13]=[C:14]([CH:18]([N:25]2[CH:29]=[C:28]([C:30]3[C:31]4[CH:38]=[CH:37][N:36]([CH2:39][O:40][CH2:41][CH2:42][Si:43]([CH3:44])([CH3:46])[CH3:45])[C:32]=4[N:33]=[CH:34][N:35]=3)[CH:27]=[N:26]2)[CH2:19][CH:20]=[O:21])[CH:15]=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 21225700DiisobutylaluminumhydrideHCID 57478001ethyl 3-(3-bromophenyl)-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanoate

Product 1

HCID 574780023-(3-bromophenyl)-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanalYield 76%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

Diisobutylaluminum hydride in hexane (1M, 4 mL) was added to a −78° C. solution of ethyl 3-(3-bromophenyl)-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanoate (600 mg, 0.001 mol) in DCM (6 mL, 0.09 mol). After stirring for 4 h, the reaction was quenched with cold methanol (300 μL), and then saturated ammonium chloride (500 μL) was added and the resulting solution was stirred for 1 h. The reaction was partitioned between water and EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated. The product was purified by flash chromatography on silica gel eluting with hexane:EtOAc, (2:1 to 1:2), to give 3-(3-bromophenyl)-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]-pyrimidin-4-yl)-1H-pyrazol-1-yl]propanal (400 mg, 70%) as an oil. 1H NMR (400 MHz, CDCl3): δ 9.9 (s, 1H), 8.9 (s, 1H), 8.4 (s, 2H), 7.6 (d, 1H), 7.5 (d, 1H), 7.4 (d, 1H), 7.3-7.4 (m, 2H), 6.8 (d, 1H), 6.1 (m, 1H), 5.7 (s, 2H), 4 (m, 1H), 3.6 (m, 2H), 3.3 (dd, 1H), 1.0 (m, 2H), 0.01 (s, 9H). m/z=526, 528 (M+1).

Workup

  1. customthe reaction was quenched with cold methanol (300 μL)
  2. additionsaturated ammonium chloride (500 μL) was added
  3. stirringthe resulting solution was stirred for 1 h
  4. customThe reaction was partitioned between water and EtOAc
  5. washThe organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe product was purified by flash chromatography on silica gel eluting with hexane

Sources & evidence

ORD record
ord-0c12bf2560ee459f8de78e9010300057
Source dataset
uspto-grants-2013_09
Patent number
US08541425B2

Reaction notes

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