Ethylenediamine → 5-{3-(cyanomethyl)-3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-[(1S)-1-cyclopropylethyl]pyrazine-2-carboxamide

HRID 2363355Notes

Reaction equation

HRID 2363355 reaction equation
[C:1]([CH2:3][C:4]1([N:22]2[CH:26]=[C:25]([C:27]3[CH:32]=[CH:31][N:30]=[C:29]4[N:33](COCC[Si](C)(C)C)[CH:34]=[CH:35][C:28]=34)[CH:24]=[N:23]2)[CH2:7][N:6]([C:8]2[N:9]=[CH:10][C:11]([C:14]([NH:16][C@H:17]([CH:19]3[CH2:21][CH2:20]3)[CH3:18])=[O:15])=[N:12][CH:13]=2)[CH2:5]1)#[N:2].C(N)CN>FC(F)(F)C(O)=O.C(Cl)Cl.CO>[C:1]([CH2:3][C:4]1([N:22]2[CH:26]=[C:25]([C:27]3[CH:32]=[CH:31][N:30]=[C:29]4[NH:33][CH:34]=[CH:35][C:28]=34)[CH:24]=[N:23]2)[CH2:7][N:6]([C:8]2[N:9]=[CH:10][C:11]([C:14]([NH:16][C@H:17]([CH:19]3[CH2:21][CH2:20]3)[CH3:18])=[O:15])=[N:12][CH:13]=2)[CH2:5]1)#[N:2]

Participants

6

Reactant 2

HCID 3301EthylenediamineHCID 711435375-{3-(cyanomethyl)-3-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-[(1S)-1-cyclopropylethyl]pyrazine-2-carboxamide

Product 1

HCID 711558525-{3-(cyanomethyl)-3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-[(1S)-1-cyclopropylethyl]pyrazine-2-carboxamideYield 72.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

5-{3-(Cyanomethyl)-3-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-[(1S)-1-cyclopropylethyl]pyrazine-2-carboxamide (0.23 g) was dissolved in a solution of trifluoroacetic acid (2 mL) and methylene chloride (2 mL). The mixture was stirred at room temperature for 2 h, and concentrated to dryness under reduced pressure. The residue was purified by flash chromatography on a silica gel column with methanol in methylene chloride (0-5%) to afford an intermediate which was dissolved in methanol (3.0 mL). To the solution was added ethylenediamine (1.0 mL). The mixture was stirred at room temperature for 2 h. The mixture was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with methanol in methylene chloride (0-5%) to afford the desired product (0.13 g). LCMS (M+H)+: m/z=468.5. 1H NMR (500 MHz, DMSO-d6): δ 12.13 (s, 1H), 8.96 (s, 1H), 8.65 (d, J=1.3 Hz, 1H), 8.44 (s, 1H), 8.30 (d, J=5.5 Hz, 1H), 8.20 (d, J=8.7 Hz, 1H), 8.00 (d, J=1.3 Hz, 1H), 7.67-7.61 (m, 1H), 7.52 (d, J=5.5 Hz, 1H), 7.09-7.04 (m, 1H), 4.82 (d, J=9.7 Hz, 2H), 4.56 (d, J=9.7 Hz, 2H), 3.77 (s, 2H), 3.50-3.28 (m, 1H), 1.22 (d, J=6.7 Hz, 3H), 1.15-0.98 (m, 1H), 0.49-0.39 (m, 1H), 0.39-0.30 (m, 1H), 0.29-0.22 (m, 1H), 0.22-0.15 (m, 1H).

Workup

  1. concentrationconcentrated to dryness under reduced pressure
  2. customThe residue was purified by flash chromatography on a silica gel column with methanol in methylene chloride (0-5%)
  3. customto afford an intermediate which
  4. stirringThe mixture was stirred at room temperature for 2 h
  5. concentrationThe mixture was concentrated under reduced pressure
  6. customThe residue was purified by flash chromatography on a silica gel column with methanol in methylene chloride (0-5%)

Sources & evidence

ORD record
ord-cf2e74e8b8344ee5a82ed93996b2b88c
Source dataset
uspto-grants-2014_04
Patent number
US08691807B2

Reaction notes

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