Trimethylsilyl isocyanate → 4-(4-{3-[1-(2,6-Dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-pyrazol-1-yl)-piperidine-1-carboxamide

HRID 2046927Notes

Reaction equation

HRID 2046927 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[CH:10]([C:12]1[C:20]2[C:15](=[N:16][CH:17]=[C:18]([C:21]3[CH:22]=[N:23][N:24]([CH:26]4[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]4)[CH:25]=3)[CH:19]=2)[NH:14][CH:13]=1)[CH3:11].C[Si]([N:36]=[C:37]=[O:38])(C)C.CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[CH:10]([C:12]1[C:20]2[C:15](=[N:16][CH:17]=[C:18]([C:21]3[CH:22]=[N:23][N:24]([CH:26]4[CH2:27][CH2:28][N:29]([C:37]([NH2:36])=[O:38])[CH2:30][CH2:31]4)[CH:25]=3)[CH:19]=2)[NH:14][CH:13]=1)[CH3:11]

Participants

5

Reactant 3

HCID 70696Trimethylsilyl isocyanateHCID 81531DiisopropylethylamineHCID 461964113-[1-(2,6-Dichloro-3-fluorophenyl)ethyl]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 673629124-(4-{3-[1-(2,6-Dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-pyrazol-1-yl)-piperidine-1-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine (8.0 mg, 0.0174 mmol), trimethylsilyl isocyanate (4.02 mg, 0.0349 mmol), DIPEA (0.02 mL, 0.09 mmol) and DCM (1 mL) was stirred at rt for 30 min. The solution was concentrated in vacuo, redissolved in MeOH and purified via HPLC. The fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ=1.89 (d, J=7.1 Hz, 3 H), 1.93-2.05 (m, 2H), 2.07-2.16 (m, 2 H), 2.95-3.06 (m, 2 H), 4.17 (d, J=13.6 Hz, 2 H), 4.41 (tt, J=11.5, 4.2 Hz, 1 H), 5.25-5.34 (m, 1 H), 7.19 (t, J=8.7 Hz, 1 H), 7.36 (d, J=1.5 Hz, 1 H), 7.38-7.52 (m, 2 H), 7.58 (s, 1 H), 7.90 (s, 1 H), 8.32 (d, J=1.8 Hz, 1 H). MS (ES+): m/z 501.02 (100) [MH+]. HPLC: tR=3.15 min (ZQ3, polar—5 min).

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. dissolutionredissolved in MeOH
  3. custompurified via HPLC
  4. additionThe fractions containing the pure product
  5. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-6d9a67db5f504088bcdf71356fef3920
Source dataset
uspto-grants-2013_11
Patent number
US08592448B2

Reaction notes

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