Potassium Carbonate → HCID 58180924, compound

HRID 1772828Notes

Reaction equation

HRID 1772828 reaction equation
[Si:1]([O:8][CH2:9][CH:10]1[N:15]([CH2:16][CH:17]=[CH:18][C:19]#[N:20])[CH2:14][CH2:13][N:12]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[NH:28]1[CH:32]=[C:31]([C:33]2[C:34]3[CH:41]=[CH:40][N:39]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[C:35]=3[N:36]=[CH:37][N:38]=2)[CH:30]=[N:29]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Si:1]([O:8][CH2:9][CH:10]1[N:15]([CH2:16][CH:17]([N:28]2[CH:32]=[C:31]([C:33]3[C:34]4[CH:41]=[CH:40][N:39]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[C:35]=4[N:36]=[CH:37][N:38]=3)[CH:30]=[N:29]2)[CH2:18][C:19]#[N:20])[CH2:14][CH2:13][N:12]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:11]1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 426313464-(1H-Pyrazol-4-yl)-7-(2-(trimethylsilyl)ethoxy)methyl-7 H-pyrrolo(2,3-d)-pyrimidineHCID 67272608HCID 67272608, compound

Product 1

HCID 58180924HCID 58180924, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of tert-butyl 3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-[3-cyanoprop-2-en-1-yl]piperazine-1-carboxylate (0.31 g, 0.78 mmol, as a mixture of E- and Z-isomers from Step 2) and 4-(1H-pyrazol-4-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (0.18 g, 0.56 mmol, prepared as described in WO 2007/070514 Example 65) in DMF (0.50 mL) was added potassium carbonate (0.23 g, 1.7 mmol). The mixture was stirred at ambient temperature overnight. The mixture was filtered, diluted with EtOAc, washed with water three times, and washed once with brine, dried over sodium sulfate, decanted and concentrated in vacuo. Flash chromatography, on a 40 g silica gel cartridge, eluting with a gradient from 0-70% EtOAc in hexanes afforded product as a mixture of diastereomers (330 mg, 83%). 1H NMR (400 MHz, CDCl3): δ 8.84 (s, 2H), 8.33-8.29 (m, 4H), 7.40 (d, 2H), 6.78 (d, 2H), 5.68 (s, 4H), 4.66-4.52 (m, 2H), 3.81-2.29 (m, 30H), 1.43 (s, 9H), 1.43 (s, 9H), 0.92 (dd, 4H), 0.91 (s, 9H), 0.87 (s, 9H), 0.09 (s, 6H), 0.04 (s, 6H), −0.06 (s, 18H); LCMS (M+H)+: 711.5.

Workup

  1. filtrationThe mixture was filtered
  2. additiondiluted with EtOAc
  3. washwashed with water three times
  4. washwashed once with brine
  5. dry with materialdried over sodium sulfate
  6. customdecanted
  7. concentrationconcentrated in vacuo
  8. washFlash chromatography, on a 40 g silica gel cartridge, eluting with a gradient from 0-70% EtOAc in hexanes afforded product as a mixture of diastereomers (330 mg, 83%)

Sources & evidence

ORD record
ord-45f0ca8e862a4d28b836e2d0b540b556
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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