Toluene → HCID 53379341, compound

HRID 1617422Notes

Reaction equation

HRID 1617422 reaction equation
[CH:1]1([CH2:5][OH:6])[CH2:4][CH2:3][CH2:2]1.C(Cl)Cl.[C:10](Cl)(Cl)=[O:11].C1(C)C=CC=CC=1.[NH:21]1[CH2:26][CH2:25][CH:24]([N:27]2[CH2:30][C:29]([CH2:53][C:54]#[N:55])([N:31]3[CH:35]=[C:34]([C:36]4[C:37]5[CH:44]=[CH:43][N:42](COCC[Si](C)(C)C)[C:38]=5[N:39]=[CH:40][N:41]=4)[CH:33]=[N:32]3)[CH2:28]2)[CH2:23][CH2:22]1.C(N(CC)C(C)C)(C)C.C(N)CN>CO>[C:54]([CH2:53][C:29]1([N:31]2[CH:35]=[C:34]([C:36]3[C:37]4[CH:44]=[CH:43][NH:42][C:38]=4[N:39]=[CH:40][N:41]=3)[CH:33]=[N:32]2)[CH2:30][N:27]([CH:24]2[CH2:25][CH2:26][N:21]([C:10]([O:6][CH2:5][CH:1]3[CH2:4][CH2:3][CH2:2]3)=[O:11])[CH2:22][CH2:23]2)[CH2:28]1)#[N:55]

Participants

9

Reactant 7

HCID 1140TolueneHCID 3301EthylenediamineHCID 6344DichloromethaneHCID 6371PhosgeneHCID 78130CyclobutylcarbinolHCID 81531DiisopropylethylamineHCID 67391103{1-piperidin-4-yl-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile

Product 1

HCID 53379341HCID 53379341, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of cyclobutylmethanol (11 μL, 0.12 mmol) in methylene chloride (1 mL, 20 mmol) was added 2.02 M phosgene in toluene (0.045 mL, 0.091 mmol). After stirred for 2 hours, {1-piperidin-4-yl-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile (0.020 g, 0.040 mmol) and N,N-diisopropylethylamine (0.040 mL, 0.23 mmol) were added and was stirred overnight. The solvent was removed by rotary evaporation to give an oil. The oil was then dissolved in 1 mL methanol and 100 microL ethylenediamine was added. After 1 hour, the reaction was purified by prep-HPLC (pH10) using a Waters XBridge C18, 5 μm particle size, 19×100 mm; mobile phase system: aqueous (0.1% NH4OH)/acetonitrile; flow rate: 30 mL/min; separation gradient: 40-60% B in 5 min to give 15 mg white solid a (78%). 1H NMR (400 MHz, DMSO): δ 12.08 (1H, br); 8.75 (1H, s); 8.62 (1H, s); 8.35 (1H, s); 7.55 (1H, m); 7.0 (1H, m); 3.9 (2H, d); 3.65 (4H, m); 3.5 (4H, m); 2.9 (2H, br); 2.38 (1H, m); 1.91 (2H, m); 1.77 (2H, m); 1.61 (5H, m); 1.03 (2H, m). LCMS (M+1): 475.

Workup

  1. stirringwas stirred overnight
  2. customThe solvent was removed by rotary evaporation
  3. customto give an oil
  4. waitAfter 1 hour
  5. customthe reaction was purified by prep-HPLC (pH10)
  6. customseparation gradient

Sources & evidence

ORD record
ord-8790222a7ae84c4da2bba2954f0a823c
Source dataset
uspto-grants-2014_07
Patent number
US08765734B2

Reaction notes

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