1,2-Dichloroethane → HCID 178491835, compound

HRID 2095678Notes

Reaction equation

HRID 2095678 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].Cl.[CH3:36][NH:37][CH3:38].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(N(CC)CC)C.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:37]([CH3:38])[CH3:36])[CH2:30][CH2:29]4)[C:26]=3[CH3:27])[CH:20]=2)[NH:15][CH:14]=1)[CH3:12]

Participants

6

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 10473Dimethylamine, hydrochlorideHCID 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 178491835HCID 178491835, 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), dimethylamine hydrochloride (20.34 mg, 0.2495 mmol), sodium triacetoxyborohydride (10.58 mg, 0.04990 mmol) and triethylamine (0.06 mL, 0.4 mmol) in 1,2-dichloroethane (3 mL, 40 mmol) was heated to 60° C. in a sealed tube for 1 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 cis and trans products separately were concentrated in vacuo to afford the title compound as white solid. 1H NMR (400 MHz, CD3OD): δ=1.42-1.65 (m, 2H), 1.82 (d, J=7.1 Hz, 3H), 1.95-2.19 (m, 6H), 2.24 (s, 3H), 2.36-2.42 (m, 6H), 2.44-2.53 (m, 1H), 3.66 (br. s., 3H), 4.13-4.26 (m, 1H), 5.12 (q, J=7.1 Hz, 1H), 6.91 (dd, J=9.0, 4.2 Hz, 1H), 7.10 (t, J=9.0 Hz, 1H), 7.36 (d, J=1.3 Hz, 1H), 7.42 (s, 1H), 7.49 (s, 1H), 8.12 (d, J=2.0 Hz, 1H). MS (ES+): m/z=510.25/512.25 (100/50) [MH+]. HPLC: tR=1.18 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 cis and trans products
  4. concentrationseparately were concentrated in vacuo

Sources & evidence

ORD record
ord-de318e0dd25b49ea9720d96eb9f8a1c6
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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