Methylamine → HCID 67388648, compound

HRID 908494Notes

Reaction equation

HRID 908494 reaction equation
CN.[NH2:3][C:4]1[C:9]([C:10]2[O:11][C:12]3[C:18]([C:19](O)=[O:20])=[CH:17][CH:16]=[CH:15][C:13]=3[N:14]=2)=[CH:8][C:7]([C:22]2[CH:23]=[N:24][N:25]([CH:27]3[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]3)[CH:26]=2)=[CH:6][N:5]=1.F[P-](F)(F)(F)(F)F.[CH3:47][N:48](C(=[O+]N1C2=NC=CC=C2N=N1)N(C)C)C>CO.CN(C=O)C>[NH2:3][C:4]1[N:5]=[CH:6][C:7]([C:22]2[CH:23]=[N:24][N:25]([CH:27]3[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]3)[CH:26]=2)=[CH:8][C:9]=1[C:10]1[O:11][C:12]2[C:18]([C:19](=[O:20])[NH:48][CH3:47])=[CH:17][CH:16]=[CH:15][C:13]=2[N:14]=1

Participants

6

Reactant 3

HCID 6329Methylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67388769HCID 67388769, compound

Product 1

HCID 67388648HCID 67388648, compoundYield 75.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A 2M solution of methylamine in methanol (0.535 ml) was added to a mixture of 2-[2-amino-5-[1-(1-tert-butoxycarbonyl-4-piperidyl)pyrazol-4-yl]-3-pyridyl]-1,3-benzoxazole-7-carboxylic acid (270 mg) and bis(dimethylamino)methylene-(triazolo[5,4-b]pyridin-3-yl)oxonium hexafluorophosphate (285 mg) dissolved in DMF (1 ml). The resulting solution was heated at 25° C. for 1 day. A 2N solution of methylamine (0.535 ml) in methanol was added and the mixture was stirred at 25° C. in a sealed tube for 3 days. The mixture was evaporated to dryness and adsorbed on silica gel. The crude product was purified by flash chromatography on silica gel eluting with 20 to 50% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford tert-butyl 4-[4-[6-amino-5-[7-(methylcarbamoyl)-1,3-benzoxazol-2-yl]-3-pyridyl]pyrazol-1-yl]piperidine-1-carboxylate (210 mg) as a pale yellow solid. NMR Spectrum: (DMSOd6) 1.43 (s, 9H), 1.80 (dd, 1H), 1.85 (dd, 1H), 2.01-2.11 (m, 2H), 2.94 (bs, 2H), 2.96 (d, 3H), 4.00-4.13 (m, 2H), 4.36-4.46 (m, 1H), 7.51 (dd, 1H), 7.65 (bs, 2H), 7.82 (dd, 1H), 7.93 (s, 1H), 7.98 (dd, 1H), 8.30 (s, 1H), 8.43 (q, 1H), 8.54 (d, 1H), 8.57 (d, 1H); Mass spectrum: M+H+ 518.

Workup

  1. customThe mixture was evaporated to dryness
  2. customThe crude product was purified by flash chromatography on silica gel eluting with 20 to 50% ethyl acetate in petroleum ether
  3. customThe solvent was evaporated to dryness

Sources & evidence

ORD record
ord-61f125a8f5884ab599a9c0f2b1b55a85
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

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