Propylphosphonic acid → N-[5-(2-Amino-7-bicyclo[1.1.1]pent-1-yl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-pyridin-3-yl]-2-(5-fluoro-pyridin-2-yl)-acetamide

HRID 82137

Reaction equation

HRID 82137 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]([C:10]2[C:18]3[CH:17]=[N:16][C:15]([NH:19]CC4C=CC(OC)=CC=4)=[N:14][C:13]=3[N:12]([C:29]34[CH2:33][CH:31]([CH2:32]3)[CH2:30]4)[CH:11]=2)=[O:9])[CH:5]=[N:6][CH:7]=1.[F:34][C:35]1[CH:36]=[CH:37][C:38]([CH2:41][C:42]([OH:44])=O)=[N:39][CH:40]=1.CCCP(O)(O)=O>C1COCC1>[NH2:19][C:15]1[N:16]=[CH:17][C:18]2[C:10]([C:8]([C:4]3[CH:3]=[C:2]([NH:1][C:42](=[O:44])[CH2:41][C:38]4[CH:37]=[CH:36][C:35]([F:34])=[CH:40][N:39]=4)[CH:7]=[N:6][CH:5]=3)=[O:9])=[CH:11][N:12]([C:29]34[CH2:32][CH:31]([CH2:33]3)[CH2:30]4)[C:13]=2[N:14]=1

Participants

5

Reactant 3

HCID 204484Propylphosphonic acidHCID 55267809(5-Fluoropyridin-2-yl)acetic acidHCID 70817455(5-amino-pyridin-3-yl)-[7-bicyclo[1.1.1]pent-1-yl-2-(4-methoxy-benzylamino)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-methanone

Product 1

HCID 70817744N-[5-(2-Amino-7-bicyclo[1.1.1]pent-1-yl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-pyridin-3-yl]-2-(5-fluoro-pyridin-2-yl)-acetamideYield 31%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (5-amino-pyridin-3-yl)-[7-bicyclo[1.1.1]pent-1-yl-2-(4-methoxy-benzylamino)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-methanone (Preparation 287) (50 mg, 0.11 mmol) in THF (5 mL) at room temperature was added 5-fluoro pyridine-2-yl acetic acid (27 mg, 0.17 mmol), TEA (0.08 mL, 0.56 mmol) and 1-propylphosphonic acid cyclic anhydride (50% solution in EtOAc, 0.20 mL, 0.34 mmol). The resulting mixture was before stirred for 18 hours. The mixture was concentrated under reduced pressure and the residue was partitioned between saturated sodium bicarbonate solution (10 mL) and ethyl acetate (25 mL). The organic phase was dried over sodium sulphate and concentrated under reduced pressure. TFA (1.5 mL) was added and the resulting mixture stirred at room temperature for 18 hours. The mixture was concentrated under reduced pressure and the residue partitioned between saturated sodium bicarbonate (10 mL) and ethyl acetate (30 mL). The organic phase was dried over sodium sulphate, concentrated under reduced pressure purified by Preparative TLC (MeOH:DCM 5:95) to afford the title compound as off white solid in 31% yield, 16 mg. 1H NMR (400 MHz, DMSO-d6) δ: 2.32 (s, 6H), 2.66 (s, 1H), 3.94 (s, 2H), 6.57 (s, 2H), 7.49 (m, 1H), 7.69-7.73 (m, 2H), 8.38 (s, 1H), 8.50 (d, 1H), 8.65 (d, 1H), 8.92 (s, 1H), 8.96 (d, 1H), 10.67 (s, 1H); LCMS (System 10): Rt=2.85 min; m/z 458 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customthe residue was partitioned between saturated sodium bicarbonate solution (10 mL) and ethyl acetate (25 mL)
  3. dry with materialThe organic phase was dried over sodium sulphate
  4. concentrationconcentrated under reduced pressure
  5. additionTFA (1.5 mL) was added
  6. stirringthe resulting mixture stirred at room temperature for 18 hours
  7. concentrationThe mixture was concentrated under reduced pressure
  8. customthe residue partitioned between saturated sodium bicarbonate (10 mL) and ethyl acetate (30 mL)
  9. dry with materialThe organic phase was dried over sodium sulphate
  10. concentrationconcentrated under reduced pressure
  11. custompurified by Preparative TLC (MeOH:DCM 5:95)

Sources & evidence

ORD record
ord-777f8e72caca43409cb5f6b7ede8c4bc
Source dataset
uspto-grants-2014_09
Patent number
US08846698B2

Linked notes

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