Methanol → HCID 57477793, compound

HRID 1524719Notes

Reaction equation

HRID 1524719 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]([N:12]2[CH:16]=[C:15]([C:17]3[C:18]4[CH:25]=[CH:24][N:23](COCC[Si](C)(C)C)[C:19]=4[N:20]=[CH:21][N:22]=3)[CH:14]=[N:13]2)[CH2:9][C:10]#[N:11])=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O.C(Cl)Cl.CO.C(N)CN>>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]([N:12]2[CH:16]=[C:15]([C:17]3[C:18]4[CH:25]=[CH:24][NH:23][C:19]=4[N:20]=[CH:21][N:22]=3)[CH:14]=[N:13]2)[CH2:9][C:10]#[N:11])=[CH:4][CH:3]=1

Participants

6

Reactant 5

HCID 887MethanolHCID 3301EthylenediamineHCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 574780983-(6-Chloropyridin-3-yl)-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile

Product 1

HCID 57477793HCID 57477793, compoundYield 69%

Procedure

3-(6-Chloropyridin-3-yl)-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]-pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile (prepared by methods analogous to those described for Example 61) (0.070 g, 0.00014 mol) in TFA (3.0 mL, 0.039 mol) and DCM (3.0 mL, 0.047 mol) was stirred at room temperature for 1 hour. Solvent was removed in vacuo, and the residue was dissolved in methanol (4.0 mL, 0.099 mol) and ethylenediamine (0.07 mL, 0.001 mol). The reaction mixture was stirred at room temperature overnight. Solvent was removed in vacuo, the crude product was purified by preparative HPLC eluting with an ACN; water gradient buffered with ammonium hydroxide to pH=10, to give 3-(6-chloropyridin-3-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile as a white powder (35 mg, 69%), LCMS (M+1)+: 350, 1H NMR (DMSO-d6) δ 12.21 (b, 1H), 9.00 (s, 1H), 8.78 (s, 1H), 8.62 (s, 1H), 8.58 (s, 1H), 8.00 (m, 1H), 7.70 (m, 2H), 7.00 (s, 1H), 6.22 (m, 1H), 3.90 (m, 1H), 3.78 (m, 1H)

Workup

  1. customSolvent was removed in vacuo
  2. customSolvent was removed in vacuo
  3. customthe crude product was purified by preparative HPLC
  4. washeluting with an ACN

Sources & evidence

ORD record
ord-d78d81f642224b2d96b880715aa38b21
Source dataset
uspto-grants-2015_07
Patent number
US09079912B2

Reaction notes

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