Benzylamine → HCID 68456803, compound

HRID 2387516Notes

Reaction equation

HRID 2387516 reaction equation
O[C:2]1[CH:7]=[CH:6][N:5]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[N:13]([CH2:17][CH2:18][N:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[N:12]=[CH:11]3)[C:4](=[O:24])[CH:3]=1.[CH2:25]([NH2:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C1(N)C(F)=C(F)C(F)=C(N)C=1F.[ClH:45].Cl>>[ClH:45].[ClH:45].[CH2:25]([NH:32][C:2]1[CH:7]=[CH:6][N:5]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[N:13]([CH2:17][CH2:18][N:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[N:12]=[CH:11]3)[C:4](=[O:24])[CH:3]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

4

Reactant 3

HCID 7504BenzylamineHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 57625508HCID 57625508, compound

Product 1

HCID 68456803HCID 68456803, compoundYield 22%

Procedure

4-Hydroxy-1-(1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazol-5-yl)pyridin-2(1H)-one (120 mg, 0.37 mmol) and benzylamine (0.3 mL) were irradiated in a microwave tube for min at 300 W. Purification by column chromatography (12 g ISCO column eluting with ethyl acetate and a methanol/ammonia mixture (10:1); gradient 100% ethyl acetate to 80% ethyl acetate over 30 min at 25 mL/min) provided the free-base. This was converted to the dihydrochloride as in Example 64 to provide the title compound (43 mg, 22%) as a yellow solid: mp 180-185° C.; 1H NMR (500 MHz, CD3OD) δ 8.25 (s, 1H), 7.90 (d, J=1.8 Hz, 1H), 7.87 (d, J=8.9 Hz, 1H), 7.75 (s, 1H), 7.51-7.49 (dd, J=8.9, 1.9 Hz, 1H), 7.40-7.39 (m, 4H), 7.33-7.30 (dd, J=8.5, 4.3 Hz, 1H), 6.63 (d, J=76 Hz, 1H), 4.90 (t, J=5.9 Hz, 2H), 4.54 (s, 2H), 3.86 (t, J=5.9 Hz, 2H), 3.77-3.68 (m, 2H), 3.18-3.13 (m, 2H), 2.17-2.13 (m, 2H), 2.03-2.00 (m, 2H); ESI MS m/z 414 [M+H]+; HPLC (Method C)>99% (AUC), tR=12.9 min.

Workup

  1. customPurification by column chromatography (12 g ISCO column
  2. washeluting with ethyl acetate
  3. customgradient 100% ethyl acetate to 80% ethyl acetate over 30 min at 25 mL/min) provided the free-base

Sources & evidence

ORD record
ord-faf654f3b92048cabd29301e856e4ebb
Source dataset
uspto-grants-2012_09
Patent number
US08268868B2

Reaction notes

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