Acetaldehyde → HCID 54760985, compound

HRID 929962Notes

Reaction equation

HRID 929962 reaction equation
Cl.[C:2]([C:6]1[O:10][N:9]=[C:8]([NH:11][C:12](=[O:36])[NH:13][C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:35])[C:22]3[CH:27]=[C:26]([O:28][CH:29]4[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]4)[CH:25]=[CH:24][N:23]=3)=[CH:16][CH:15]=2)[CH:7]=1)([CH3:5])([CH3:4])[CH3:3].[CH:37](=O)[CH3:38].[BH3-]C#N.[Na+]>CO.CC([O-])=O.[Na+]>[C:2]([C:6]1[O:10][N:9]=[C:8]([NH:11][C:12](=[O:36])[NH:13][C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:35])[C:22]3[CH:27]=[C:26]([O:28][CH:29]4[CH2:30][CH2:31][N:32]([CH2:37][CH3:38])[CH2:33][CH2:34]4)[CH:25]=[CH:24][N:23]=3)=[CH:16][CH:15]=2)[CH:7]=1)([CH3:5])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 177AcetaldehydeHCID 5003444Sodium cyanoborohydrideHCID 54589424HCID 54589424, compound

Product 1

HCID 54760985HCID 54760985, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 23696304HCID 23696304, compoundSolvent

Procedure

To a stirred solution of N-(4-(3-(5-tert-butylisoxazol-3-yl)ureido)phenyl)-4-(piperidin-4-yloxy)picolinamide hydrochloride from Example 1 (100 mg, 0.19 mmol) in 2 mL of pH˜4 MeOH/NaOAc buffer (21 grams of NaOAc.3H2O and 48 mL of AcOH, diluted to 1.0 L with methanol) was added acetaldehyde (0.2 mL, excess) and NaCNBH3 (25 mg, excess). The resulting mixture was stirred at rt for 3 h. LC-MS indicated that the reaction was complete. The crude product was purified by reverse phase HPLC to afford N-(4-(3-(5-tert-butylisoxazol-3-yl)ureido)phenyl)-4-(1-ethylpiperidin-4-yloxy)picolinamide as a white powder (52 mg, 53% yield). LC-MS (ESI) m/z 507 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ 10.55 (s, 1H), 9.49 (s, 1H), 8.79 (s, 1H), 8.54 (d, J=5.65 Hz, 1H), 7.83 (d, J=9.04 Hz, 2H), 7.67 (br. s., 1H), 7.43 (d, J=8.85 Hz, 2H), 7.26 (dd, J=2.45, 5.65 Hz, 1H), 6.50 (s, 1H), 4.82 (br. s., 1H), 2.75-3.14 (m, 3H), 2.07 (br. s., 2H), 1.75 (br. s., 2H), 1.30 (s, 9H), 1.13 (br. s., 3H).

Workup

  1. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-c734a2bdc4214ea891d5d8ad0bb1a5c2
Source dataset
uspto-grants-2016_03
Patent number
US09296722B2

Reaction notes

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