Cesium carbonate → 6-(7-Cycloheptyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-nicotinic acid

HRID 1850531Notes

Reaction equation

HRID 1850531 reaction equation
[CH3:1][N:2]([CH3:22])[C:3]([C:5]1[N:14]([CH:15]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)[C:8]2[N:9]=[C:10](Cl)[N:11]=[CH:12][C:7]=2[CH:6]=1)=[O:4].C[O:24][C:25](=[O:33])[C:26]1[CH:31]=[CH:30][C:29]([NH2:32])=[N:28][CH:27]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:15]1([N:14]2[C:8]3[N:9]=[C:10]([NH:32][C:29]4[CH:30]=[CH:31][C:26]([C:25]([OH:33])=[O:24])=[CH:27][N:28]=4)[N:11]=[CH:12][C:7]=3[CH:6]=[C:5]2[C:3](=[O:4])[N:2]([CH3:22])[CH3:1])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 737487Methyl 6-aminonicotinateHCID 866866262-chloro-7-cycloheptyl-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide

Product 1

HCID 673554046-(7-Cycloheptyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-nicotinic acidYield 44.2%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
130 °C

Procedure

To a mixture of 2-Chloro-7-cycloheptyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (517 mg, 1.2 mmol, 1.0 eq), 6-Amino-nicotinic acid methyl ester (221 mg, 1.5 mmol, 1.2 eq), Cs2CO3 (591 mg, 1.8 mmol, 1.5 eq) and BINAP (38 mg, 0.06 mmol, 0.05 eq) was bubbled in N2 via a pipette for 3 min. Pd(OAc)2 (14 mg, 0.06 mmol, 0.05 eq) was added and the flask was sealed and stirred in an oil bath heated to 130° C. for 3 hr. The mixture was filtered through a pad of celite and washed with etOAc. The organic layer was washed with water, then brine and the organic layers combined, dried over Na2SO4. The solvent was evaporated and the brown solid was triturated with acetonitrile, filtered, washed with ACN and dried under high vacuum to yield the title compound as a light pink solid (236 mg, 0.53 mmol, 44% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 8.84-8.90 (m, 1H) 8.69 (s, 1H) 8.61 (d, J=9.09 Hz, 1H) 8.51 (br s, 1H) 8.20-8.26 (m, 1H) 6.40 (s, 1H) 4.40-4.53 (m, 1H) 3.87 (s, 3H) 3.10 (s, 6H) 2.48-2.64 (m, 2H) 1.90-2.00 (m, 2H) 1.76-1.86 (m, 2H) 1.63-1.72 (m, 4H) 1.45-1.56 (m, 2H). MS (m/z, MH+): 437.5

Workup

  1. customwas bubbled in N2 via a pipette for 3 min
  2. customthe flask was sealed
  3. filtrationThe mixture was filtered through a pad of celite
  4. washwashed with etOAc
  5. washThe organic layer was washed with water
  6. dry with materialdried over Na2SO4
  7. customThe solvent was evaporated
  8. customthe brown solid was triturated with acetonitrile
  9. filtrationfiltered
  10. washwashed with ACN
  11. customdried under high vacuum

Sources & evidence

ORD record
ord-57c931cc2e844d48bfd7c6b5844a1bad
Source dataset
uspto-grants-2015_02
Patent number
US08957074B2

Reaction notes

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