Acetic Acid → HCID 68224169, compound

HRID 1400963Notes

Reaction equation

HRID 1400963 reaction equation
[CH:1]1([NH:4][C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[CH:29]=[CH:28][C:27]([CH:30]=O)=[CH:26][N:25]=5)[S:23][C:16]=34)=[C:10]([F:32])[CH:9]=2)=[O:6])[CH2:3][CH2:2]1.[NH2:33][CH:34]1[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:36][CH2:35]1.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.CN(C=O)C>[CH:1]1([NH:4][C:5](=[O:6])[NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[N:25]=[CH:26][C:27]([CH2:30][NH:33][CH:34]6[CH2:35][CH2:36][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:38][CH2:39]6)=[CH:28][CH:29]=5)[S:23][C:16]=34)=[C:10]([F:32])[CH:9]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 12682914-Amino-1-Boc-piperidineHCID 5049666Sodium triacetoxyborohydrideHCID 582365791-Cyclopropyl-3-(3-fluoro-4-(2-(5-formylpyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)urea

Product 1

HCID 68224169HCID 68224169, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of aldehyde 47 (0.3 g, 0.669 mmol) in a mixture of DCM (9 mL) and DMF (3 mL) were added 4-amino—Boc-piperidine (0.27 g, 1.34 mmol) and acetic acid (80 μL, 1.34 mmol) at RT. The reaction mixture was stirred for 1.5 hr, treated with NaBH(OAc)3 (0.425 g, 2.00 mmol) and stirred overnight, then quenched by addition of saturated NaHCO3 solution and extracted with DCM/MeOH. The extract was washed with brine, dried over MgSO4 and concentrated. The residue was purified by flash chromatography on silica gel (EtOAc/MeOH: 93/7 to 84/16) to afford title compound 607 (0.355 g, 84% yield) as a pale brown solid. 1H NMR (300 MHz, DMSO-d6) δ (ppm): 8.69 (s, 1H), 8.58 (brs, 1H), 8.51 (d, J=5.7 Hz, 1H), 8.30 (s, 1H), 8.22 (d, J=8.1 Hz, 1H), 7.91 (dd, J=8.4, 1.8 Hz, 1H), 7.72 (dd, J=13.5, 1.8 Hz, 1H), 7.37 (t, J=9.0 Hz, 1H), 7.25-7.15 (m, 1H), 6.64 (d, J=5.4 Hz, 1H), 6.55 (d, J=2.7 Hz, 1H), 3.85-3.75 (m, 2H), 3.81 (s, 2H), 2.90-2.65 (m, 2H), 1.85-1.75 (m, 2H), 1.45-1.35 (m, 1H), 1.39 (s, 9H), 1.25-1.10 (m, 2H), 0.71-0.62 (m, 2 Hz, 0.48-0.40 (m, 2H).

Workup

  1. stirringstirred overnight
  2. customquenched by addition of saturated NaHCO3 solution
  3. extractionextracted with DCM/MeOH
  4. washThe extract was washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography on silica gel (EtOAc/MeOH: 93/7 to 84/16)

Sources & evidence

ORD record
ord-ab4941d45b124752a918db7fad9b376a
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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