Phosphoric Acid → tert-butyl 3-{[5-fluoro-2-(methoxymethyl)pyrimidin-4-yl]amino}-6,6-dimethyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxylate

HRID 331083Notes

Reaction equation

HRID 331083 reaction equation
[NH2:1][C:2]1[C:3]2[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C:7]([CH3:18])([CH3:17])[C:4]=2[NH:5][N:6]=1.Cl[C:20]1[C:25]([F:26])=[CH:24][N:23]=[C:22]([CH2:27][O:28][CH3:29])[N:21]=1.[K].OP(O)(O)=O>CS(C)=O>[F:26][C:25]1[C:20]([NH:1][C:2]2[C:3]3[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C:7]([CH3:18])([CH3:17])[C:4]=3[NH:5][N:6]=2)=[N:21][C:22]([CH2:27][O:28][CH3:29])=[N:23][CH:24]=1

Participants

6

Reactant 4

HCID 1004Phosphoric AcidHCID 5462222PotassiumHCID 401519444-Chloro-5-fluoro-2-(methoxymethyl)pyrimidineHCID 40152088tert-Butyl 3-amino-6,6-dimethyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxylate

Product 1

HCID 57519207tert-butyl 3-{[5-fluoro-2-(methoxymethyl)pyrimidin-4-yl]amino}-6,6-dimethyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxylate

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of tert-butyl 3-amino-6,6-dimethyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxylate (3.00 g, 11.6 mmol) and 4-chloro-5-fluoro-2-(methoxymethyl)pyrimidine (2.06 g, 11.6 mmol) in DMSO (8 mL) was added potassium dihygrogenphosphate (1.58 g, 2.3 mmol) followed by H3PO4 (0.29 g, 2.3 mmol). The reaction was place in a 90° C. oil bath and heated for 20 h. The crude reaction was cooled to room temperature then poured into ice cold NaHCO3 (60 mL) and extracted with EtOAc (2×30 mL). The combined organic extracts were washed with brine then dried (MgSO4), filtered and concentrated. The crude solid was triturated with EtOAc to provide the title compound N1(i) as a white solid (3.2 g, 70%). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.44 (s, 9H), 1.59 (s, 3H), 1.61 (s, 3H), 3.34 (s, 3H), 4.29-4.44 (m, 2H), 4.45-4.64 (m, 2H), 8.32 (d, J=3.20 Hz, 1H), 10.25 (br. s., 1H), 12.24 (br. s., 1H). Mass Spectrum: Calcd for C18H25FN6O3(M+H): 393. Found: 393.

Workup

  1. customin a 90° C.
  2. temperatureheated for 20 h
  3. customThe crude reaction
  4. extractionextracted with EtOAc (2×30 mL)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialthen dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude solid was triturated with EtOAc

Sources & evidence

ORD record
ord-67279843fa3d4d6c9771a185e129433f
Source dataset
uspto-grants-2014_11
Patent number
US08877761B2

Reaction notes

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