Triethylamine → HCID 58180975, compound

HRID 1772806Notes

Reaction equation

HRID 1772806 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9]=[O:10])=[C:4]([CH3:11])[CH:3]=1.Cl.[N:13]1([CH2:19][CH:20]([N:24]2[CH:28]=[C:27]([C:29]3[C:30]4[CH:37]=[CH:36][N:35](COCC[Si](C)(C)C)[C:31]=4[N:32]=[CH:33][N:34]=3)[CH:26]=[N:25]2)[CH2:21][C:22]#[N:23])[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.C(N(CC)CC)C>C1COCC1>[N:32]1[C:31]2[NH:35][CH:36]=[CH:37][C:30]=2[C:29]([C:27]2[CH:26]=[N:25][N:24]([CH:20]([CH2:21][C:22]#[N:23])[CH2:19][N:13]3[CH2:18][CH2:17][N:16]([C:9]([NH:8][C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=4[CH3:11])=[O:10])[CH2:15][CH2:14]3)[CH:28]=2)=[N:34][CH:33]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1241417167191-92-8HCID 670549114-piperazin-1-yl-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile hydrochloride

Product 1

HCID 58180975HCID 58180975, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-Fluoro-1-isocyanato-2-methylbenzene (10 mg, 0.068 mmol) was added to a solution of 4-piperazin-1-yl-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile hydrochloride (20 mg, 0.034 mmol; from Example 12, Step 2) and triethylamine (28 uL, 0.20 mmol) in THF (0.39 mL). The reaction was stirred for one hour, then solvent was removed in vacuo. The residue was stirred in a 1:1 mixture of DCM:TFA for 1 hour, concentrated, and stirred in a solution of methanol (1 mL) containing ethylenediamine (0.2 mL) for one hour. Purification via preparative HPLC-MS, eluting with a gradient of MeCN/H2O containing 0.15% NH4OH afforded product as the free base (11 mg, 67%). 1H NMR (400 MHz, d6-dmso): δ 12.12 (br s, 1H), 8.82 (s, 1H), 8.69 (s, 1H), 8.38 (s, 1H), 8.01 (s, 1H), 7.61 (d, 1H), 7.11 (dd, 1H), 7.02 (dd, 1H), 6.98 (d, 1H), 6.92 (dt, 1H), 5.01 (tt, 1H), 3.42-3.29 (m, 4H), 3.26-3.19 (m, 2H), 2.86 (dd, 1H), 2.81 (dd, 1H), 2.54-2.46 (m, 2H), 2.43-2.34 (m, 2H), 2.11 (s, 3H); LCMS (M+H)+: 488.3.

Workup

  1. customsolvent was removed in vacuo
  2. stirringThe residue was stirred in a 1:1 mixture of DCM
  3. waitTFA for 1 hour
  4. concentrationconcentrated
  5. stirringstirred in a solution of methanol (1 mL)
  6. additioncontaining ethylenediamine (0.2 mL) for one hour
  7. customPurification via preparative HPLC-MS
  8. washeluting with a gradient of MeCN/H2O containing 0.15% NH4OH afforded product as the free base (11 mg, 67%)

Sources & evidence

ORD record
ord-626b63c31265440388208a100bfbdc4a
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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