Methanol → HCID 178488509, compound

HRID 1042001Notes

Reaction equation

HRID 1042001 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8]([C:20]3[NH:21][C:22]4[C:27]([CH:28]=3)=[CH:26][CH:25]=[CH:24][C:23]=4[O:29][CH3:30])[N:9]=[C:10]([C@H:11]3[CH2:16][CH2:15][C@H:14]([C:17]([OH:19])=[O:18])[CH2:13][CH2:12]3)[N:6]2[N:5]=[CH:4][N:3]=1.C(O)C[CH2:33][OH:34].C[OH:37]>>[NH2:21][C:22]([CH2:23][OH:29])([CH2:27][OH:37])[CH2:33][OH:34].[NH2:1][C:2]1[C:7]2=[C:8]([C:20]3[NH:21][C:22]4[C:27]([CH:28]=3)=[CH:26][CH:25]=[CH:24][C:23]=4[O:29][CH3:30])[N:9]=[C:10]([C@H:11]3[CH2:16][CH2:15][C@H:14]([C:17]([OH:19])=[O:18])[CH2:13][CH2:12]3)[N:6]2[N:5]=[CH:4][N:3]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 104421,3-PropanediolHCID 178488508HCID 178488508, compound

Product 1

HCID 178488509HCID 178488509, compoundYield 70.2%

Procedure

The compound trans-4-[4-Amino-5-(7-methoxy-1H-indol-2-yl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclohexanecarboxylic acid can be prepared as known in the art, e.g., according to US 2007/0112005 (Example 258 thereof). This product (5.01 g, 12.3 mmol) was suspended in MeOH (75.0 mL) and heated to reflux. 1,3-Propanediol, 2-amino-2-(hydroxymethyl) (1.79 g, 14.8 mmol) was added and the reaction was heated at reflux for 1 h. The suspension was allowed to cool to RT and then filtered. The solid was washed with MeOH and then dried in vacuo overnight at 50° C. to provide the title compound as a tan solid (4.57 g, 70.2% yield). 1H NMR (400 MHz, CD3OD): δ 1.67 (dddd, J=12.8, 12.8, 12.8, 2.8 Hz, 2H), 1.87 (dddd, J=13.2, 13.2, 13.2, 3.2 Hz, 2H), 2.14-2.17 (m, 4H), 234 (tt, J=12.4, 2.8 Hz, 1H), 3.40 (tt, J=12.4, 3.2 Hz, 1H), 3.65 (s, 6H), 4.01 (s, 3H), 6.75 (d, J=7.2 Hz, 1H), 6.75 (s, 1H), 7.04 (dd, J=7.6, 7.6 Hz, 1H), 7.23 (d, J=7.6 Hz, 1H), 7.88 (s, 1H). 13C NMR (100 MHz, DMSO): δ 29.1, 29.6, 34.3, 43.9, 55.3, 59.0, 61.3, 102.3, 102.5, 110.9, 113.1, 120.1, 126.8, 127.2, 130.0, 132.1, 146.3, 146.7, 178.6. LCMS (ESI+): m/z 407 (MH+). Anal. Calcd. for C25H33N7O6: C, 56.92%; H, 6.30%; N, 18.58%; O, 18.20%. Found: C, 56.23%; H, 6.31%; N, 18.33%; O, 18.63%.

Workup

  1. temperatureheated to reflux
  2. temperaturethe reaction was heated
  3. temperatureat reflux for 1 h
  4. filtrationfiltered
  5. washThe solid was washed with MeOH
  6. customdried in vacuo overnight at 50° C.

Sources & evidence

ORD record
ord-112d4dbdbbfa480b9aa512b3c3af6a6b
Source dataset
uspto-grants-2013_10
Patent number
US08557814B2

Reaction notes

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