1-Butanol → HCID 178463607, compound

HRID 1192527Notes

Reaction equation

HRID 1192527 reaction equation
[F:1][C:2]1[CH:11]=[C:10]([CH:12]([NH2:14])[CH3:13])[C:9]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[N:7]2.[NH2:22][C:23]1[N:31]=[C:30]2[C:26]([NH:27][CH:28]=[N:29]2)=[C:25](Br)[N:24]=1.C(O)CCC.C(N(CC)C(C)C)(C)C>>[F:1][C:2]1[CH:11]=[C:10]([CH:12]([NH:14][C:25]2[N:24]=[C:23]([NH2:22])[N:31]=[C:30]3[C:26]=2[N:27]=[CH:28][NH:29]3)[CH3:13])[C:9]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[N:7]2

Participants

5

Reactant 4

HCID 2631-ButanolHCID 81531DiisopropylethylamineHCID 61011392-Amino-6-bromopurineHCID 58368432HCID 58368432, compound

Product 1

HCID 178463607HCID 178463607, compound

Conditions

Temperature
120 °C

Procedure

A solution of 1-[5-fluoro-8-(3-fluorophenyl)cinnolin-7-yl]ethanamine (73 mg, 0.26 mmol) [from peak 1 of Examples 20 and 21, step B] and 2-amino-6-bromopurine (82 mg, 0.38 mmol) in 1-butanol (0.51 mL, 5.6 mmol) was treated with N,N-diisopropylethylamine (67 μL, 0.38 mmol), degassed with nitrogen for 5 minutes and stirred at 120° C. for 18 hours. The reaction mixture was diluted with methanol (10 mL), stirred and filtered. The filtrate was purified first by RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 60 mL/minute) and then by RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/minute) to give the desired product in 26%. LCMS for C21H17F2N8 (M+H)+: m/z=419.2; Found: 418.9. 1H NMR (300 MHz, DMSO-d6): δ 12.1 (br s, 1H), 9.44 (d, J=5.9 Hz, 1H), 8.25-8.22 (m, 1H), 8.13-8.01 (m, 1H), 7.94-7.83 (m, 1H), 7.72-7.53 (m, 3H), 7.40-7.29 (m, 1H), 7.28-7.22 (m, 1H), 5.45-5.21 (m, 3H), 1.42-1.38 (m, 3H).

Workup

  1. customdegassed with nitrogen for 5 minutes
  2. additionThe reaction mixture was diluted with methanol (10 mL)
  3. stirringstirred
  4. filtrationfiltered
  5. customThe filtrate was purified first by RP-HPLC (XBridge C18 column
  6. washeluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 60 mL/minute) and then by RP-HPLC (XBridge C18 column
  7. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/minute)

Sources & evidence

ORD record
ord-362c46aa67054c809123da7d2634b202
Source dataset
uspto-grants-2014_03
Patent number
US08680108B2

Reaction notes

Loading…