Aluminium lithium hydride → 2-(4-{3-[(S)-1-(2,6-Dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]-pyridin-5-yl}-pyrazol-1-yl)-2-methylpropan-1-ol

HRID 2046945Notes

Reaction equation

HRID 2046945 reaction equation
C[O:2][C:3](=O)[C:4]([N:7]1[CH:11]=[C:10]([C:12]2[CH:13]=[C:14]3[C:20]([C@@H:21]([C:23]4[C:28]([Cl:29])=[CH:27][CH:26]=[C:25]([F:30])[C:24]=4[Cl:31])[CH3:22])=[CH:19][NH:18][C:15]3=[N:16][CH:17]=2)[CH:9]=[N:8]1)([CH3:6])[CH3:5].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[Cl:31][C:24]1[C:25]([F:30])=[CH:26][CH:27]=[C:28]([Cl:29])[C:23]=1[C@H:21]([C:20]1[C:14]2[C:15](=[N:16][CH:17]=[C:12]([C:10]3[CH:9]=[N:8][N:7]([C:4]([CH3:5])([CH3:6])[CH2:3][OH:2])[CH:11]=3)[CH:13]=2)[NH:18][CH:19]=1)[CH3:22]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 673629092-(4-{3-[(S)-1-(2,6-Dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-pyrazol-1-yl)-2-methylpropionic acid methyl ester

Product 1

HCID 673639632-(4-{3-[(S)-1-(2,6-Dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]-pyridin-5-yl}-pyrazol-1-yl)-2-methylpropan-1-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 2-(4-{3-[(S)-1-(2,6-Dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]-pyridin-5-yl}-pyrazol-1-yl)-2-methylpropionic acid methyl ester (64.0 mg, 0.135 mmol) in THF (3.0 mL) was added 2 M of LiAlH4 in THF (0.20 mL, 0.40 mmol) under N2 at −78° C. The reaction mixture was stirred for 1 h at −78° C., quenched by adding water, warmed to rt, filtered, and concentrated in vacuo. Purification of the residue by HPLC afforded the title compound. A crystal structure of the title compound bound to cMet confirmed the absolute configuration as shown. 1H NMR (400 MHz, CD3OD): δ=1.58 (s, 6 H), 1.88 (d, J=7.2 Hz, 3 H), 3.75 (s, 2 H), 5.28 (q, J=7.2 Hz, 1H), 7.18 (t, J=8.6 Hz, 1 H), 7.35 (d, J=1.3 Hz, 1 H), 7.37-7.39 (m, 1H), 7.41 (brs, 1H), 7.58 (s, 1 H), 7.91 (s, 1 H), 8.32 (d, J=1.8 Hz, 1H). MS (ES+): m/z 447.09/449.04 (100/70) [MH+]. HPLC: tR=3.50 min (ZQ3 polar—5 min).

Workup

  1. customquenched
  2. additionby adding water
  3. temperaturewarmed to rt
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by HPLC

Sources & evidence

ORD record
ord-9d019e8fd8bc415e99bedd53689cbbb2
Source dataset
uspto-grants-2013_11
Patent number
US08592448B2

Reaction notes

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