Acetaldehyde → HCID 118029272, compound

HRID 58143Notes

Reaction equation

HRID 58143 reaction equation
O[C:2]([C:4](F)(F)F)=O.[Cl:8][C:9]1[C:14]([O:15][CH3:16])=[CH:13][C:12]([O:17][CH3:18])=[C:11]([Cl:19])[C:10]=1[NH:20][C:21](=[O:48])[N:22]([C:24]1[N:29]=[CH:28][N:27]=[C:26]([NH:30][C:31]2[CH:36]=[CH:35][C:34]([CH:37]3[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]3)=[CH:33][C:32]=2[NH:43][C:44](=[O:47])[CH:45]=[CH2:46])[CH:25]=1)[CH3:23].CC([O-])=O.[Na+].C(=O)C.[BH3-]C#N.[Na+]>CCO>[Cl:19][C:11]1[C:12]([O:17][CH3:18])=[CH:13][C:14]([O:15][CH3:16])=[C:9]([Cl:8])[C:10]=1[NH:20][C:21](=[O:48])[N:22]([C:24]1[N:29]=[CH:28][N:27]=[C:26]([NH:30][C:31]2[CH:36]=[CH:35][C:34]([CH:37]3[CH2:42][CH2:41][N:40]([CH2:2][CH3:4])[CH2:39][CH2:38]3)=[CH:33][C:32]=2[NH:43][C:44](=[O:47])[CH:45]=[CH2:46])[CH:25]=1)[CH3:23]

Participants

6

Reactant 4

HCID 177AcetaldehydeHCID 517045Sodium AcetateHCID 5003444Sodium cyanoborohydrideHCID 121317888HCID 121317888, compound

Product 1

HCID 118029272HCID 118029272, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of N-(2-(6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-ylamino)-5-(piperidin-4-yl)phenyl)acrylamide TFA salt (35 g, 0.049 mmol) in EtOH (1 mL), was added NaOAc (4 g, 0.05 mmol) and aqueous acetaldehyde (1 mL, 0.9 mmol, 40%). After the mixture was stirred at room temperature for 1 hour, NaBH3CN (12 g, 0.18 mmol) was added, and the solution was stirred at room temperature for another 3 hours. After removal of all volatiles in vacuo, the residue was partitioned between DCM and water. The aqueous layer was extracted with chloroform twice. The combined extracts were washed with brine, dried over anhydrous Na2SO4 and filtered. The filtrate was evaporated under vacuum to give crude product, which was purified by prep-HPLC to afford the title compound (3 mg, yield: 10%). 1H NMR (400 MHz, MeOH-d4) δ 8.38 (s, 1H), 7.68 (s, 1H), 7.54 (d, 1H), 7.24 (dd, 1H), 6.83 (s, 1H), 6.46-6.35 (m, 3H), 5.81 (d, 1H), 3.97 (s, 6H), 3.74-3.70 (m, 2H), 3.37 (s, 3H), 3.26 (q, 2H), 3.17-3.11 (m, 2H), 2.99-2.96 (m, 1H), 2.26-2.22 (m, 2H), 2.06-1.99 (m, 2H), 1.43 (t, 3H); MS (ESI): 628 [M+H]+.

Workup

  1. stirringthe solution was stirred at room temperature for another 3 hours
  2. customAfter removal of all volatiles in vacuo
  3. customthe residue was partitioned between DCM and water
  4. extractionThe aqueous layer was extracted with chloroform twice
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. customThe filtrate was evaporated under vacuum
  9. customto give crude product, which
  10. customwas purified by prep-HPLC

Sources & evidence

ORD record
ord-becfe4ab20a349c4a2a39155084acdef
Source dataset
uspto-grants-2016_09
Patent number
US09434697B2

Reaction notes

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