Methanol → HCID 57477793, compound

HRID 1843519Notes

Reaction equation

HRID 1843519 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)□ δ12.21 (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-4c235dee65f045cabc9e8128af3a2023
Source dataset
uspto-grants-2015_02
Patent number
US08946245B2

Reaction notes

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