Acetic Acid → HCID 23653422, compound

HRID 1094907Notes

Reaction equation

HRID 1094907 reaction equation
[NH:1]1[CH2:6][CH2:5]OC[CH2:2]1.[CH2:7]=O.[NH2:9][C:10]1[C:15]2=[C:16]([C:20]3[CH:25]=[CH:24][C:23]([NH:26][C:27]([NH:29][C:30]4[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][N:31]=4)=[O:28])=[C:22]([F:40])[CH:21]=3)[C:17]([CH3:19])=[CH:18][N:14]2[N:13]=[CH:12][N:11]=1.[CH3:41][C:42]([OH:44])=O>CCOC(C)=O>[NH2:9][C:10]1[C:15]2=[C:16]([C:20]3[CH:25]=[CH:24][C:23]([NH:26][C:27]([NH:29][C:30]4[CH:35]=[C:34]([C:36]([F:38])([F:37])[F:39])[CH:33]=[CH:32][N:31]=4)=[O:28])=[C:22]([F:40])[CH:21]=3)[C:17]([CH3:19])=[C:18]([CH2:7][N:1]3[CH2:2][CH2:41][CH2:42][O:44][CH2:5][CH2:6]3)[N:14]2[N:13]=[CH:12][N:11]=1

Participants

6

Reactant 4

HCID 176Acetic Acid2×HCID 712FormaldehydeHCID 8083MorpholineHCID 579552711-[4-(4-Amino-6-methylpyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-fluorophenyl]-3-[4-(trifluoromethyl)pyridin-2-yl]urea

Product 1

HCID 23653422HCID 23653422, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Morpholine (196 mg, 2.25 mmol) was added to Acetic acid (1 mL) and the mixture vigorously shaken for 5 min. The resulting mixture was treated with 37% aq formaldehyde (67 mg, 2.24 mmol) and stirred until homogeneous. The resulting solution was treated with a solution of 1-[4-(4-amino-6-methylpyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-fluorophenyl]-3-[4-(trifluoromethyl)pyridin-2-yl]urea in 2 mL AcOH and the mixture heated at 80° C. for 14 h. The reaction was diluted with EtOAc (50 mL) and washed with sodium carbonate solution. The organic layer was dried with sodium sulfate and concentrated under vacuum. The resulting solid was taken up in 1 mL MeOH with the aid of TFA (50 uL). Purification by preparative RP-HPLC provided the desired product (41.1 mg, 34%) as a white solid. 1H-NMR (DMSO-d6) δ 10.25 (s, 1H), 10.19 (bs, 1H), 9.98 (bs, 1H), 8.63 (d, 1H, J=5 Hz), 8.36-8.44 (m, 1H), 8.11 (s, 1H), 8.09 (s, 1H), 7.43-7.50 (m, 1H), 7.38 (dd, 1H, J=12, 2 Hz), 7.24 (dd, 1H, J=8, 1 Hz), 4.78 (s, 2H), 3.97-4.08 (m, 2H), 3.68-3.81 (m, 1H), 3.40-3.55 (m, 2H), 3.23-3.45 (m, 2H), 2.27 (s, 3H); MS [M+H]+=545.1; LCMS RT=2.56 min.

Workup

  1. stirringstirred until homogeneous
  2. washwashed with sodium carbonate solution
  3. dry with materialThe organic layer was dried with sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customPurification by preparative RP-HPLC

Sources & evidence

ORD record
ord-acbcc2a4ef794dccbef2658bc4cd4745
Source dataset
uspto-grants-2012_03
Patent number
US08133995B2

Reaction notes

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