1,2-Dichloroethane → HCID 178491834, compound

HRID 2095681Notes

Reaction equation

HRID 2095681 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([O:9][CH3:10])[C:3]=1[C@H:11]([C:13]1[C:21]2[C:16](=[N:17][CH:18]=[C:19]([C:22]3[CH:23]=[N:24][N:25]([CH:28]4[CH2:33][CH2:32][C:31](=O)[CH2:30][CH2:29]4)[C:26]=3[CH3:27])[CH:20]=2)[NH:15][CH:14]=1)[CH3:12].[C:35]([N:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1)(=[O:37])[CH3:36].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].ClCCCl>>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([O:9][CH3:10])[C:3]=1[C@H:11]([C:13]1[C:21]2[C:16](=[N:17][CH:18]=[C:19]([C:22]3[CH:23]=[N:24][N:25]([C@@H:28]4[CH2:33][CH2:32][C@H:31]([N:41]5[CH2:42][CH2:43][N:38]([C:35](=[O:37])[CH3:36])[CH2:39][CH2:40]5)[CH2:30][CH2:29]4)[C:26]=3[CH3:27])[CH:20]=2)[NH:15][CH:14]=1)[CH3:12]

Participants

5

Reactant 4

HCID 111,2-DichloroethaneHCID 837951-AcetylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 546746704-(4-{3-[(1S)-1-(2-chloro-3-fluoro-6-methoxyphenyl)ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-5-methyl-1H-pyrazol-1-yl)cyclohexanone

Product 1

HCID 178491834HCID 178491834, compound

Conditions

Temperature
60 °C

Procedure

A mixture of 4-(4-{3-[(1S)-1-(2-chloro-3-fluoro-6-methoxyphenyl)ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-5-methyl-1H-pyrazol-1-yl)cyclohexanone (12.0 mg, 0.0250 mmol), 1-acetylpiperazine (31.98 mg, 0.2495 mmol), sodium triacetoxyborohydride (10.58 mg, 0.04990 mmol) and 1,2-dichloroethane (3 mL, 40 mmol) was heated to 60° C. in a sealed tube for 6 h. The solution was extracted with DCM and sat. NaHCO3, and the organic layer was loaded onto silica gel for column chromatography, eluting with 3-7% (7N NH3 in MeOH)/DCM. The fractions containing the product were concentrated in vacuo to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ=1.63-1.73 (m, 3H), 1.81 (d, J=7.1 Hz, 3H), 2.00 (s, 3H), 2.10-2.14 (m, 4H), 2.25-2.43 (m, 4H), 2.58-2.66 (m, 4H), 3.59-3.70 (m, 8H), 4.34 (tdd, J=9.3, 9.3, 4.7, 4.3 Hz, 1H), 5.12 (q, J=6.8 Hz, 1H), 6.90 (dd, J=9.1, 4.3 Hz, 1H), 7.09 (t, J=8.8 Hz, 1H), 7.36 (d, J=1.0 Hz, 1H), 7.42 (s, 1H), 7.47 (s, 1H), 8.12 (s, 1H). MS (ES+): m/z=593.27/595.27 (100/50) [MH+]. HPLC: tR=1.19 min (polar—3 min, UPLC-ACQUITY).

Workup

  1. extractionThe solution was extracted with DCM and sat. NaHCO3
  2. washeluting with 3-7% (7N NH3 in MeOH)/DCM
  3. additionThe fractions containing the product
  4. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-290308c53a4247c996b07afe25dfadda
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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