m-Toluidine → HCID 86695820, compound

HRID 338693Notes

Reaction equation

HRID 338693 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][N:10]([C:12]3[CH:20]=[CH:19][C:15]([C:16]([OH:18])=O)=[CH:14][CH:13]=3)[CH2:9][CH2:8][C:6]=2[N:7]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[C:57]([CH3:61])[CH:56]=1>CN(C=O)C>[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][N:10]([C:12]3[CH:20]=[CH:19][C:15]([C:16]([NH:54][C:55]4[CH:56]=[C:57]([CH3:61])[CH:58]=[CH:59][CH:60]=4)=[O:18])=[CH:14][CH:13]=3)[CH2:9][CH2:8][C:6]=2[N:7]=1

Participants

6

Reactant 4

HCID 7934m-ToluidineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86695819HCID 86695819, compound

Product 1

HCID 86695820HCID 86695820, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzoic acid (27 mg, 0.10 mmol), N,N-diisopropylethylamine (0.087 mL, 0.50 mmol), and HBTU (42 mg, 0.11 mmol) in 1.0 mL DMF was stirred at room temperature for 10 minutes. Then meta-toluidine (0.022 mL, 0.20 mmol) was added and the reaction heated at 55° C. for 18 hours. The reaction mixture was partitioned between EtOAc and aqueous Na2CO3 solution, the EtOAc layer washed with H2O, brine, dried with anhydrous Na2SO4 and rotary evaporated. The resulting solid was triturated with an EtOAc/hexane mixture to give the title compound as a light beige solid (18 mg, 51%). 1H NMR (DMSO-d6) δ: 9.84 (s, 1H), 8.12 (s, 1H), 7.85-7.92 (m, 2H), 7.60 (s, 1H), 7.55 (d, J=8.2 Hz, 1H), 7.19 (t, J=7.8 Hz, 1H), 7.03-7.09 (m, 2H), 6.88 (d, J=7.6 Hz, 1H), 6.42 (s, 2H), 4.36 (s, 2H), 3.71 (t, J=6.0 Hz, 2H), 2.75 (t, J=5.9 Hz, 2H), 2.30 (s, 3H)

Workup

  1. temperaturethe reaction heated at 55° C. for 18 hours
  2. customThe reaction mixture was partitioned between EtOAc and aqueous Na2CO3 solution
  3. washthe EtOAc layer washed with H2O, brine
  4. dry with materialdried with anhydrous Na2SO4 and rotary evaporated
  5. customThe resulting solid was triturated with an EtOAc/hexane mixture

Sources & evidence

ORD record
ord-07d002a01be6457198580231916a5d86
Source dataset
uspto-grants-2014_11
Patent number
US08889870B2

Reaction notes

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