Pivalic acid → HCID 59272467, compound

HRID 558157Notes

Reaction equation

HRID 558157 reaction equation
[N:1]1([CH2:6][CH2:7][NH:8][C:9]2[N:14]=[C:13]([C:15]3[S:19][C:18]4[C:20]([C:24]5[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=5C(=O)C)=[CH:21][CH:22]=[CH:23][C:17]=4[CH:16]=3)[C:12]([F:34])=[CH:11][N:10]=2)[CH:5]=[CH:4][N:3]=[N:2]1.C[C:36](C)(C)[C:37]([OH:39])=O.[CH3:42][NH:43][CH2:44][CH2:45]O.C([BH3-])#N>O1CCOCC1>[NH3:1].[N:1]1([CH2:6][CH2:7][NH:8][C:9]2[N:14]=[C:13]([C:15]3[S:19][C:18]4[C:20]([C:24]5[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=5[CH:44]([N:43]([CH3:42])[CH2:36][CH2:37][OH:39])[CH3:45])=[CH:21][CH:22]=[CH:23][C:17]=4[CH:16]=3)[C:12]([F:34])=[CH:11][N:10]=2)[CH:5]=[CH:4][N:3]=[N:2]1

Participants

7

Reactant 4

HCID 6417Pivalic acidHCID 80162-(Methylamino)ethanol2×HCID 498716Cyano-borohydrideHCID 66999942HCID 66999942, compound

Product 2

HCID 222AmmoniaYield 10%HCID 59272467HCID 59272467, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
160 °C

Procedure

Combine 1-(2-(2-(2-(2-(1H-1,2,3-triazol-1-yl)ethylamino)-5-fluoropyrimidin-4-yl)benzo[b]thiophen-7-yl)-4-fluorophenyl)ethanone (0.1 g, 0.21 mmol), 10% trimethylacetic acid in dioxane (2 mL), 2-(methylamino)ethanol (18.2 mg, 0.252 mmol) and silica-supported cyanoborohydride (0.276 g, 0.262 mmol). Heat the reaction mixture at 160° C. for 2 h in a microwave reactor. Add 2-(methylamino)ethanol (0.157 g, 2.1 mmol) and silica-supported cyanoborohydride (0.138 g, 0.131 mmol). Heat the reaction mixture at 160° C. for 4 h in a microwave reactor. Pour the crude reaction mixture onto a strong cation exchange (SCX) (10 g) column. Elute with 2 N methanolic ammonia (40 mL) and concentrate. Purify the residue by normal phase chromatography (0-100% B at 25 mL/minute for 25 minutes on a 12 g silica column, Solvent A: DCM, Solvent B: 10% 2 N methanolic ammonia in DCM) to give the title compound (41 mg, 36%). MS (ES) m/z 536 [M+1]+.

Workup

  1. temperatureHeat the reaction mixture at 160° C. for 4 h in a microwave reactor
  2. additionPour the crude
  3. customreaction mixture onto a strong cation exchange (SCX) (10 g) column
  4. washElute with 2 N methanolic ammonia (40 mL)
  5. concentrationconcentrate
  6. customPurify the residue by normal phase chromatography (0-100% B at 25 mL/minute for 25 minutes on a 12 g silica column, Solvent A

Sources & evidence

ORD record
ord-bacbf79c04694b4395a448055a363b0b
Source dataset
uspto-grants-2011_11
Patent number
US08063035B2

Reaction notes

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