Acetic Acid → HCID 66738579, compound

HRID 2047208Notes

Reaction equation

HRID 2047208 reaction equation
[CH3:1][C@@H:2]1[CH2:7][CH:6]([NH2:8])[CH2:5][C@H:4]([CH3:9])[O:3]1.[CH3:10][Si:11]([CH3:49])([CH3:48])[CH2:12][CH2:13][O:14][CH2:15][N:16]([CH2:40][O:41][CH2:42][CH2:43][Si:44]([CH3:47])([CH3:46])[CH3:45])[C:17]1[N:22]2[N:23]=[CH:24][C:25]([C:26]3[CH:27]=[N:28][C:29]4[C:34]([CH:35]=3)=[CH:33][C:32]([F:36])=[CH:31][CH:30]=4)=[C:21]2[N:20]=[C:19]([CH:37]=O)[C:18]=1[Br:39].CC(O)=O.[BH3-]C#N.[Na+]>ClCCCl.C(O)C.C(Cl)Cl>[Br:39][C:18]1[C:19]([CH2:37][NH:8][CH:6]2[CH2:5][C@H:4]([CH3:9])[O:3][C@H:2]([CH3:1])[CH2:7]2)=[N:20][C:21]2[N:22]([N:23]=[CH:24][C:25]=2[C:26]2[CH:27]=[N:28][C:29]3[C:34]([CH:35]=2)=[CH:33][C:32]([F:36])=[CH:31][CH:30]=3)[C:17]=1[N:16]([CH2:40][O:41][CH2:42][CH2:43][Si:44]([CH3:45])([CH3:46])[CH3:47])[CH2:15][O:14][CH2:13][CH2:12][Si:11]([CH3:48])([CH3:49])[CH3:10]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 667335321251772-69-6HCID 86664791HCID 86664791, compound

Product 1

HCID 66738579HCID 66738579, compoundYield 30%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To crude (2R,6S)-2,6-dimethyltetrahydro-2H-pyran-4-amine (0.18 g) in DCE (4.2 ml) and Ethanol (4.2 ml) was added 7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-bromo-3-(6-fluoroquinolin-3-yl)pyrazolo[1,5-a]pyrimidine-5-carbaldehyde (0.19 g, 0.3 mmol) followed by AcOH (0.03 ml, 0.6 mmol). After stirring for 30 minutes at room temperature, NaBH3CN (37.8 mg, 0.6 mmol) was added and stirring was continued further for 30 minutes more. LC/MS showed no starting material remaining. After the solvent was rotoevaporated, the crude was dissolved with DCM (20 ml), washed with sat. NaHCO3 (1×5 ml), water (1×5 ml), brine (1×5 ml), dried over MgSO4. Solvent was removed in vacuo and the residue was purified by column chromatography on silica gel. Elution with EtOAc/Hexanes (0-60%) gave desired 6-bromo-5-(((2R,6S)-2,6-dimethyltetrahydro-2H-pyran-4-ylamino)methyl)-3-(6-fluoroquinolin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (68 mg, 30%).

Workup

  1. stirringstirring
  2. waitwas continued further for 30 minutes
  3. washwashed with sat. NaHCO3 (1×5 ml), water (1×5 ml), brine (1×5 ml)
  4. dry with materialdried over MgSO4
  5. customSolvent was removed in vacuo
  6. customthe residue was purified by column chromatography on silica gel
  7. washElution with EtOAc/Hexanes (0-60%)

Sources & evidence

ORD record
ord-7f0159e39aae4f298948814ab096e6f9
Source dataset
uspto-grants-2013_11
Patent number
US08591943B2

Reaction notes

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