Diisopropyl diazene-1,2-dicarboxylate → 5-chloro-N2-(2-methoxy-4-(1-methyl-1H-tetrazol-5-yl)phenyl)-N4-methylpyrimidine-2,4-diamine

HRID 1630350Notes

Reaction equation

HRID 1630350 reaction equation
[Cl:1][C:2]1[C:3]([NH:21][CH3:22])=[N:4][C:5]([NH:8][C:9]2[CH:18]=[CH:17][C:12]([C:13]([NH:15][CH3:16])=O)=[CH:11][C:10]=2[O:19][CH3:20])=[N:6][CH:7]=1.N1C=CC=CC=1P(C1C=CC=CC=1)C1C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.C1(P([N:70]=[N+:71]=[N-:72])(C2C=CC=CC=2)=O)C=CC=CC=1>C(OCC)(=O)C>[Cl:1][C:2]1[C:3]([NH:21][CH3:22])=[N:4][C:5]([NH:8][C:9]2[CH:18]=[CH:17][C:12]([C:13]3[N:15]([CH3:16])[N:72]=[N:71][N:70]=3)=[CH:11][C:10]=2[O:19][CH3:20])=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 199401P,P-Diphenylphosphinic azideHCID 6218932-PyridyldiphenylphosphineHCID 547560294-(5-Chloro-4-(methylamino)pyrimidin-2-ylamino)-3-methoxy-N-methylbenzamide

Product 1

HCID 715770595-chloro-N2-(2-methoxy-4-(1-methyl-1H-tetrazol-5-yl)phenyl)-N4-methylpyrimidine-2,4-diamineYield 38%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

A mixture of 4-(5-chloro-4-(methylamino)pyrimidin-2-ylamino)-3-methoxy-N-methylbenzamide (112 mg, 0.35 mmol) and 2-pyridyl diphenylphosphine (373 mg, 1.42 mmol) was flushed with N2 for 10 min Anhydrous THF (2 mL) was added followed by dropwise addition of diisopropyl azodicarboxylate (0.28 mL, 1.42 mmol). Diphenylphosphoryl azide (0.31 mL, 1.42 mmol) was added dropwise over 5 min. The mixture was heated at 45° C. under N2 for 18 h. The mixture was diluted with ethyl acetate (20 mL) and washed with saturated sodium hydrogen carbonate solution (2×10 mL). The combined aqueous washes were back-extracted with ethyl acetate (10 mL), and the combined organic extracts filtered through a hydrophobic frit and evaporated. Purification of the residue via silica gel column chromatography (0-100% ethyl acetate/isohexane) followed by trituration with diethyl ether gave 5-chloro-N2-(2-methoxy-4-(1-methyl-1H-tetrazol-5-yl)phenyl)-N4-methylpyrimidine-2,4-diamine as a white solid (45 mg, 38%). LCMS (10 cm_ESCI_Bicarb_MeCN): [MH+]=347 at 2.67 min. 1H NMR (400 MHz, CDCl3): δ 8.76 (d, J=8.5, 1H); 7.96 (s, 1H); 7.75 (s, 1H); 7.40 (d, J=1.9, 1H); 7.3 (d, J=2.0, 1H); 5.35 (s, 1H); 4.21 (s, 3H); 4.00 (s, 3H); 3.13 (d, J=4.9, 3H).

Workup

  1. customwas flushed with N2 for 10 min Anhydrous THF (2 mL)
  2. additionwas added
  3. washwashed with saturated sodium hydrogen carbonate solution (2×10 mL)
  4. extractionThe combined aqueous washes were back-extracted with ethyl acetate (10 mL)
  5. filtrationthe combined organic extracts filtered through a hydrophobic frit
  6. customevaporated
  7. customPurification of the residue via silica gel column chromatography (0-100% ethyl acetate/isohexane)

Sources & evidence

ORD record
ord-b074dd92461544348183ccc343daf817
Source dataset
uspto-grants-2014_07
Patent number
US08791130B2

Reaction notes

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