Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → HCID 69418526, compound

HRID 1375086Notes

Reaction equation

HRID 1375086 reaction equation
[CH3:1][C:2]1[C:7]2[N:8]=[C:9]([NH:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[CH3:18])[O:10][C:6]=2[CH:5]=[C:4]([CH2:19][C:20](O)=[O:21])[CH:3]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.FC(F)(F)C(O)=O.[CH3:54][O:55][C:56](=[O:71])[CH2:57][C:58]1([C:64]2[CH:69]=[CH:68][C:67]([NH2:70])=[CH:66][CH:65]=2)[CH2:63][CH2:62][O:61][CH2:60][CH2:59]1>CN(C)C=O.C(N(C(C)C)CC)(C)C>[CH3:54][O:55][C:56](=[O:71])[CH2:57][C:58]1([C:64]2[CH:65]=[CH:66][C:67]([NH:70][C:20](=[O:21])[CH2:19][C:4]3[CH:3]=[C:2]([CH3:1])[C:7]4[N:8]=[C:9]([NH:11][C:12]5[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=5[CH3:18])[O:10][C:6]=4[CH:5]=3)=[CH:68][CH:69]=2)[CH2:59][CH2:60][O:61][CH2:62][CH2:63]1

Participants

6

Reactant 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 18188094HCID 18188094, compoundHCID 69420032HCID 69420032, compound

Product 1

HCID 69418526HCID 69418526, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 81531DiisopropylethylamineSolvent2×

Procedure

A stirred solution of (4-methyl-2-o-tolylamino-benzoxazol-6-yl)-acetic acid [0.44 g, prepared according to the procedure described in International Patent Application No. WO00/61580 for Reference Example 9] in dry dimethylformamide (10 mL), under argon, was treated with O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (0.8477 g) and then with diisopropylethylamine (1.05 mL). After stirring at room temperature for 10 minutes the bright yellow solution was added to a solution of [4-{4-amino-phenyl}-tetrahydro-pyran-4-yl]-acetic acid methyl ester trifluoroacetate (0.444 g, Reference Example 18) in a mixture of dimethylformamide (8 mL) and diisopropylethylamine (1.05 mL). The mixture was stirred at room temperature under argon overnight and then evaporated to low bulk. The residue was dissolved in ethyl acetate and this solution was washed with water, then with aqueous sodium bicarbonate solution, and then with water and then evaporated. The residue was subjected to reverse phase HPLC on a Hypersil Elite C18 column using as the mobile phase a mixture of acetonitrile, water and trifluoroacetic acid (35:65:0.1, v/v/v) followed by a 1% acetonitrile/minute gradient to give the title compound (0.178 g, approximately 90% purity) which was used without further purification. LC-MS: RT=3.71 minutes, MS(ES+): 528(M+H)+.

Workup

  1. stirringThe mixture was stirred at room temperature under argon overnight
  2. customevaporated to low bulk
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washthis solution was washed with water
  5. customwith aqueous sodium bicarbonate solution, and then with water and then evaporated
  6. additiona mixture of acetonitrile, water and trifluoroacetic acid (35:65:0.1, v/v/v)

Sources & evidence

ORD record
ord-5171c14d1ee04a21a5c584976aafd1eb
Source dataset
uspto-grants-2007_01
Patent number
US07166616B2

Reaction notes

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