Potassium Carbonate → HCID 67054966, compound

HRID 1772841Notes

Reaction equation

HRID 1772841 reaction equation
[C:1]([CH:3]=[CH:4][CH2:5][N:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH:7]1[CH:19]([F:21])[F:20])#[N:2].[NH:22]1[CH:26]=[C:25]([C:27]2[C:28]3[CH:35]=[CH:34][N:33]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[C:29]=3[N:30]=[CH:31][N:32]=2)[CH:24]=[N:23]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:1]([CH2:3][CH:4]([N:22]1[CH:26]=[C:25]([C:27]2[C:28]3[CH:35]=[CH:34][N:33]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[C:29]=3[N:30]=[CH:31][N:32]=2)[CH:24]=[N:23]1)[CH2:5][N:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])[CH2:8][CH:7]1[CH:19]([F:21])[F:20])#[N:2]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 426313464-(1H-Pyrazol-4-yl)-7-(2-(trimethylsilyl)ethoxy)methyl-7 H-pyrrolo(2,3-d)-pyrimidineHCID 67054990HCID 67054990, compound

Product 1

HCID 67054966HCID 67054966, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of tert-butyl 4-[3-cyanoprop-2-en-1-yl]-3-(difluoromethyl)piperazine-1-carboxylate (0.12 g, 0.40 mmol from Step 5) and 4-(1H-pyrazol-4-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (0.12 g, 0.40 mmol, prepared as described in WO 2007/070514, Example 65) and potassium carbonate (0.16 g, 1.2 mmol) in DMF (0.36 mL) was stirred for 4.5 h. The mixture was then filtered, the filtrate was diluted with EtOAc, washed with water (thrice), brine, dried over sodium sulfate, decanted and concentrated. Flash chromatography on a 40 g silica gel cartridge eluting with a gradient of 0-80% solvent mixture [A] in hexanes ([A]=10% IPA: 50% EtOAc: 40% Hexanes) afforded a purified product (130 mg, 53%). 1H NMR (300 MHz, CDCl3): δ 8.83 (s, 2H), 8.33-8.28 (m, 4H), 7.42-7.38 (d, 2H), 6.79-6.76 (d, 2H), 5.89 (td, 1H), 5.63 (td, 1H), 5.67 (s, 4H), 4.57 (tt, 2H), 4.18-1.10 (m, 26H), 1.45, 1.43, 1.40 (3s, together 18H), 0.92 (dd, 4H), −0.08 (s, 18H); LCMS (M+H)+: 617.3.

Workup

  1. filtrationThe mixture was then filtered
  2. additionthe filtrate was diluted with EtOAc
  3. washwashed with water (thrice), brine
  4. dry with materialdried over sodium sulfate
  5. customdecanted
  6. concentrationconcentrated
  7. washFlash chromatography on a 40 g silica gel cartridge eluting with a gradient of 0-80% solvent mixture [A] in hexanes ([A]=10% IPA

Sources & evidence

ORD record
ord-c7e6b65e51b740408bbc918a47ae6aa5
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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