Acetic Acid → HCID 123448882, compound

HRID 1497661Notes

Reaction equation

HRID 1497661 reaction equation
[C:1]([O:5][C:6](=[O:48])[NH:7][CH2:8][C:9]1[CH:14]=[C:13]([C:15]2[S:19][C:18]([CH:20]3[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)=[N:17][C:16]=2[C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([N:32]([S:36]([C:39]3[CH:44]=[C:43]([F:45])[CH:42]=[CH:41][C:40]=3[F:46])(=[O:38])=[O:37])[CH2:33][O:34][CH3:35])[C:27]=2[F:47])[CH:12]=[CH:11][N:10]=1)([CH3:4])([CH3:3])[CH3:2].[C:49](O)(=O)C.C=O.C([BH3-])#N.[Na+]>CO>[C:1]([O:5][C:6](=[O:48])[NH:7][CH2:8][C:9]1[CH:14]=[C:13]([C:15]2[S:19][C:18]([CH:20]3[CH2:25][CH2:24][N:23]([CH3:49])[CH2:22][CH2:21]3)=[N:17][C:16]=2[C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([N:32]([S:36]([C:39]3[CH:44]=[C:43]([F:45])[CH:42]=[CH:41][C:40]=3[F:46])(=[O:37])=[O:38])[CH2:33][O:34][CH3:35])[C:27]=2[F:47])[CH:12]=[CH:11][N:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 131734222HCID 131734222, compound

Product 1

HCID 123448882HCID 123448882, compoundYield 52.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Tert-butyl-{4-[4-(3-{[(2,5-difluorophenyl)sulfonyl](methoxymethyl)amino}-2-fluorophenyl)-2-(piperidin-4-yl)-1,3-thiazol-5-yl]pyridin-2-yl}methylcarbamate (65 mg, 0.09 mmol) was dissolved in MeOH (5 mL) and glacial acetic acid (15 μL, 0.26 mmol). 37% aqueous formaldehyde (6.5 μL, 0.13 mmol) and sodium cyanoborohydride (8.5 mg, 0.17 mmol) were then added to the mixture, that was stirred at r.t. for 1 h. The solvent was removed under reduced pressure and the residue partitioned between ethyl acetate and 15% aqueous ammonia. The organic phase was dried over Na2SO4 and evaporated to dryness, to give 34 mg of tert-butyl-{4-[4-(3-{[(2,5-difluorophenyl)sulfonyl](methoxymethyl)amino}-2-fluorophenyl)-2-(1-methylpiperidin-4-yl)-1,3-thiazol-5-yl]pyridin-2-yl}methylcarbamate that were employed for the next step without any further purification.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue partitioned between ethyl acetate and 15% aqueous ammonia
  3. dry with materialThe organic phase was dried over Na2SO4
  4. customevaporated to dryness

Sources & evidence

ORD record
ord-e737b1fe33f34639bcea8d016f73750a
Source dataset
uspto-grants-2015_12
Patent number
US09199979B2

Reaction notes

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