Methanol → HCID 57477793, compound
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]=1Participants
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
- customSolvent was removed in vacuo
- customSolvent was removed in vacuo
- customthe crude product was purified by preparative HPLC
- washeluting with an ACN
Sources & evidence
- ORD record
- ord-1315275a8cd2466aab2ae637a6cf4936
- Source dataset
- uspto-grants-2015_01
- Patent number
- US08933086B2
Reaction notes
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