Sodium cyanoborohydride → HCID 66588113, compound

HRID 1408172Notes

Reaction equation

HRID 1408172 reaction equation
[CH3:1][N:2]([CH2:46][CH2:47][N:48]1[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]1)[C:3](=[O:45])[C:4]1[CH:44]=[CH:43][CH:42]=[C:6]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)=[CH:12][C:11]=2[C:22]2[CH:27]=[C:26]([C:28](=[O:41])[NH:29][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:39])[F:38])[CH:32]=3)[CH:25]=[CH:24][N:23]=2)=[O:8])[CH:5]=1.[BH3-][C:55]#N.[Na+]>C=O.C(O)(=O)C.C(=O)(O)[O-].[Na+]>[CH3:1][N:2]([CH2:46][CH2:47][N:48]1[CH2:53][CH2:52][N:51]([CH3:55])[CH2:50][CH2:49]1)[C:3](=[O:45])[C:4]1[CH:44]=[CH:43][CH:42]=[C:6]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)=[CH:12][C:11]=2[C:22]2[CH:27]=[C:26]([C:28](=[O:41])[NH:29][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:39])([F:40])[F:38])[CH:32]=3)[CH:25]=[CH:24][N:23]=2)=[O:8])[CH:5]=1

Participants

6

Reactant 2

HCID 5003444Sodium cyanoborohydrideHCID 66588053HCID 66588053, compound

Product 1

HCID 66588113HCID 66588113, compoundYield 9%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 712FormaldehydeSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
25 °C

Procedure

Into a 50-mL round bottom flask, was placed a solution of N1-methyl-N1-(2-(piperazin-1-yl)ethyl)-N3-(4-(piperidin-1-yl)-2-(4-(3-(trifluoromethyl)benzylcarbamoyl)pyridin-2-yl)phenyl)isophthalamide (150 mg, 0.21 mmol, 1.00 equiv) in HCHO (in water) (6 mL), NaBH3CN (15 mg, 1.10 equiv), and acetic acid (5 drops). The resulting solution was stirred for 2 h at 25° C. The resulting solution was diluted with 5 mL of sodium bicarbonate, extracted with 2×5 mL of dichloromethane, and the organic layers combined. The resulting mixture was washed with 1×5 mL of water and 1×5 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product (80 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 13.3 mg (9%) of a light yellow solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 8.96 (d, J=5.1 Hz, 1H), 8.76 (d, J=9.3 Hz, 1H), 8.45 (s, 1H), 8.15 (s, 1H), 8.05 (s, 2H), 7.89˜7.87 (m, 1H), 7.71˜7.62 (m, 5H), 7.59˜7.56 (m, 2H), 4.72 (s, 2H), 3.79 (s, 2H), 3.66 (d, J=5.1 Hz, 4H), 3.50˜3.34 (m, 2H), 3.15˜3.04 (m, 6H), 2.89˜2.85 (m, 6H), 2.80˜2.60 (m, 2H), 2.04 (d, J=4.5 Hz, 4H), 1.83 (d, J=5.4 Hz, 2H). MS (ES, m/z): 742 [M+H]+.

Workup

  1. customInto a 50-mL round bottom flask, was placed
  2. extractionextracted with 2×5 mL of dichloromethane
  3. washThe resulting mixture was washed with 1×5 mL of water and 1×5 mL of brine
  4. dry with materialThe mixture was dried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe crude product (80 mg) was purified by reverse phase HPLC
  7. washeluting with a water/CH3CN gradient
  8. additioncontaining 0.05% TFA

Sources & evidence

ORD record
ord-7aca2d9c14a64426acec511a30331941
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

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