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

HRID 2046926Notes

Reaction equation

HRID 2046926 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].[CH:32](O)=[O:33].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.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]([CH:32]=[O:33])[CH2:30][CH2:31]4)[CH:25]=3)[CH:19]=2)[NH:14][CH:13]=1)[CH3:11]

Participants

6

Reactant 4

HCID 284Formic AcidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 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 866574934-(4-{3-[1-(2,6-Dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-pyrazol-1-yl)-piperidine-1-carbaldehyde

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), formic acid (1.3 μL, 0.0349 mmol), TBTU (11.2 mg, 0.0349 mmol), DIPEA (20 μL, 0.09 mmol) and DCM (1 mL) was stirred at rt for 30 min. The solution was concentrated in vacuo, redissolved in MeOH (0.5 mL) 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=1.88 (d, J=7.1 Hz, 3 H), 1.90-2.07 (m, 2 H), 2.10-2.23 (m, 2 H), 2.90 (td, J=12.9, 2.9 Hz, 1 H), 3.32-3.37 (m, 1 H), 3.89 (ddd, J=13.5, 2.2, 2.0 Hz, 1 H), 4.41-4.56 (m, 2 H), 5.28 (q, J=7.2 Hz, 1 H), 7.18 (t, J=8.6 Hz, 1 H), 7.30-7.53 (m, 3 H), 7.58 (s, 1 H), 7.90 (s, 1 H), 8.07 (s, 1 H), 8.31 (d, J=1.8 Hz, 1H). MS (ES+): m/z 486.00 (100) [MH+]. HPLC: tR=3.30 min (ZQ3, polar—5 min).

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. dissolutionredissolved in MeOH (0.5 mL)
  3. custompurified via HPLC
  4. additionThe fractions containing the pure product
  5. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-6738ac60f65d4074b87593a5b3d4b036
Source dataset
uspto-grants-2013_11
Patent number
US08592448B2

Reaction notes

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