Isopropylamine → 4-{3-(cyanomethyl)-3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-3-fluoro-N-isopropylbenzamide

HRID 571513Notes

Reaction equation

HRID 571513 reaction equation
[CH:1]([N:4](CC)C(C)C)([CH3:3])[CH3:2].[C:10]([CH2:12][C:13]1([N:27]2[CH:31]=[C:30]([C:32]3[CH:37]=[CH:36][N:35]=[C:34]4[NH:38][CH:39]=[CH:40][C:33]=34)[CH:29]=[N:28]2)[CH2:16][N:15]([C:17]2[CH:25]=[CH:24][C:20]([C:21](O)=[O:22])=[CH:19][C:18]=2[F:26])[CH2:14]1)#[N:11].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CC(N)C.C([O-])(O)=O.[Na+]>C(Cl)Cl>[C:10]([CH2:12][C:13]1([N:27]2[CH:31]=[C:30]([C:32]3[CH:37]=[CH:36][N:35]=[C:34]4[NH:38][CH:39]=[CH:40][C:33]=34)[CH:29]=[N:28]2)[CH2:16][N:15]([C:17]2[CH:25]=[CH:24][C:20]([C:21]([NH:4][CH:1]([CH3:3])[CH3:2])=[O:22])=[CH:19][C:18]=2[F:26])[CH2:14]1)#[N:11]

Participants

7

Reactant 5

HCID 6363IsopropylamineHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 516892Sodium BicarbonateHCID 711435574-{3-(cyanomethyl)-3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-3-fluorobenzoic acid

Product 1

HCID 711435724-{3-(cyanomethyl)-3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-3-fluoro-N-isopropylbenzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N,N-Diisopropylethylamine (63 μL, 0.36 mmol) was added to a mixture of 4-{3-(cyanomethyl)-3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-3-fluorobenzoic acid (50.0 mg, 0.120 mmol), and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (64 mg, 0.14 mmol) and 2-propanamine (11 mg, 0.18 mmol) in methylene chloride (10 mL). The reaction mixture was stirred at room temperature overnight. The reaction mixture was worked up with aqueous NaHCO3, and extracted with dichloromethylene (2×10 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by RP-HPLC (pH=10) to afford the desired product. LCMS (M+H)+: m/z=458.1.

Workup

  1. extractionextracted with dichloromethylene (2×10 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by RP-HPLC (pH=10)

Sources & evidence

ORD record
ord-2974dd72cc9c42bebfcc701a23b7498f
Source dataset
uspto-grants-2015_05
Patent number
US09023840B2

Reaction notes

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