1,2-Dichloroethane → HCID 178422171, compound

HRID 2095722Notes

Reaction equation

HRID 2095722 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([O:9][CH:10]([F:12])[F:11])[C:3]=1[C@H:13]([C:15]1[C:23]2[C:18](=[N:19][CH:20]=[C:21]([C:24]3[CH:25]=[N:26][N:27]([CH:30]4[CH2:35][CH2:34][C:33](=O)[CH2:32][CH2:31]4)[C:28]=3[CH3:29])[CH:22]=2)[NH:17][CH:16]=1)[CH3:14].Cl.C[O:39][C:40](=[O:44])[CH2:41][NH:42][CH3:43].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].ClCCCl.C(N(CC)CC)C.O.[OH-].[Li+].CO>>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([O:9][CH:10]([F:12])[F:11])[C:3]=1[C@H:13]([C:15]1[C:23]2[C:18](=[N:19][CH:20]=[C:21]([C:24]3[CH:25]=[N:26][N:27]([C@H:30]4[CH2:35][CH2:34][C@H:33]([N:42]([CH3:43])[CH2:41][C:40]([OH:44])=[O:39])[CH2:32][CH2:31]4)[C:28]=3[CH3:29])[CH:22]=2)[NH:17][CH:16]=1)[CH3:14]

Participants

8

Reactant 7

HCID 111,2-DichloroethaneHCID 887MethanolHCID 8471TriethylamineHCID 83544Glycine, N-methyl-, methyl ester, hydrochloride (1:1)HCID 168937Lithium hydroxide, monohydrateHCID 5049666Sodium triacetoxyborohydrideHCID 546737614-[4-(3-{(1S)-1-[2-Chloro-6-(difluoromethoxy)-3-fluorophenyl]ethyl}-1H-pyrrolo[2,3-b]pyridin-5-yl)-5-methyl-1H-pyrazol-1-yl]cyclohexanone

Product 1

HCID 178422171HCID 178422171, compound

Conditions

Temperature
50 °C

Procedure

To a mixture of 4-[4-(3-{(1S)-1-[2-chloro-6-(difluoromethoxy)-3-fluorophenyl]ethyl}-1H-pyrrolo[2,3-b]pyridin-5-yl)-5-methyl-1H-pyrazol-1-yl]cyclohexanone (15.0 mg, 0.0290 mmol), sarcosine methyl ester hydrochloride (20.25 mg, 0.1451 mmol), sodium triacetoxyborohydride (12.30 mg, 0.05803 mmol) and 1,2-dichloroethane (4 mL, 50 mmol) was added triethylamine (14.68 mg, 0.1451 mmol), and the reaction was heated to 50° C. overnight. The material was partitioned between DCM and water, and the organic layer was concentrated in vacuo. Lithium hydroxide monohydrate (6.088 mg, 0.1451 mmol) and MeOH (2 mL, 50 mmol) were added, and the mixture was heated to 50° C. for 3 h. The solution was concentrated in vacuo, and the crude product was redissolved in minimal DMF. The solution was purified via HPLC, and the fractions containing the separate cis and trans products were concentrated in vacuo to afford the title compound as white solid. 1H NMR (400 MHz, CD3OD): δ=1.75-1.89 (m, 5H), 2.01-2.14 (m, 4H), 2.18-2.23 (m, 2H), 2.23 (s, 3H), 2.90 (s, 3H), 3.40 (tdd, J=12.0, 12.0, 3.1, 2.8 Hz, 1H), 3.65 (br. s., 2H), 4.22-4.34 (m, 1H), 5.06-5.14 (m, 1H), 6.43 (br. s., 1H), 7.12 (dd, J=8.3, 4.3 Hz, 1H), 7.18 (t, J=8.6 Hz, 1H), 7.37 (d, J=1.8 Hz, 1H), 7.40 (d, J=1.3 Hz, 1H), 7.49 (s, 1H), 8.12 (d, J=2.0 Hz, 1H). MS (ES+): m/z=590.14/592.17 (100/50) [MH+]. HPLC: tR=1.01 min (polar—2 min, UPLC-ACQUITY).

Workup

  1. customThe material was partitioned between DCM and water
  2. concentrationthe organic layer was concentrated in vacuo
  3. temperaturethe mixture was heated to 50° C. for 3 h
  4. concentrationThe solution was concentrated in vacuo
  5. dissolutionthe crude product was redissolved in minimal DMF
  6. customThe solution was purified via HPLC
  7. additionthe fractions containing the separate cis and trans products
  8. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-05fbdd82ccfd4082987e489b2ee4464f
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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