Acetic Acid → HCID 50913934, compound

HRID 475884Notes

Reaction equation

HRID 475884 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:18]2[CH2:21][C:20]([F:23])([F:22])[CH2:19]2)[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:6]=2[N:7]=1.[Cl:24][C:25]1[N:29]=[CH:28][N:27]([C:30]2[CH:36]=[CH:35][C:33]([NH2:34])=[CH:32][C:31]=2[O:37][CH3:38])[N:26]=1.C(O)(=O)C>C1COCC1.CO>[Cl:24][C:25]1[N:29]=[CH:28][N:27]([C:30]2[CH:36]=[CH:35][C:33]([NH:34][C:2]3[N:3]=[C:4]([N:18]4[CH2:19][C:20]([F:23])([F:22])[CH2:21]4)[C:5]4[CH2:10][CH2:9][CH:8]([C:11]5[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=5)[C:6]=4[N:7]=3)=[CH:32][C:31]=2[O:37][CH3:38])[N:26]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 58075503HCID 58075503, compoundHCID 580757292-chloro-4-(3,3-difluoroazetidin-1-yl)-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine

Product 1

HCID 50913934HCID 50913934, compoundYield 49.22%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-chloro-4-(3,3-difluoroazetidin-1-yl)-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine (Preparation Ha) (170 mg, 0.500 mmol) and 4-(3-chloro-1H-1,2,4-triazol-1-yl)-3-methoxyaniline (Preparation F) (146 mg, 0.650 mmol) in THF (1498 mL) was added Acetic Acid (1498 mL). The resulting mixture was heated to 100° C. and stirred overnight. The reaction mixture was then concentrated in vacuo. MeOH was added to the residue which resulted in a suspension. This was filtered to give a solid which was taken up in hot MeOH and filtered. The filtrate was then concentrated in vacuo to give N-(4-(3-chloro-1H-1,2,4-triazol-1-yl)-3-methoxyphenyl)-4-(3,3-difluoroazetidin-1-yl)-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-amine (racemate) (130 mg, 49.22% yield) as a yellow solid. LC-MS (M+H)+=528.1. 1H NMR (500 MHz, MeOD) δ ppm 8.81 (1H, s), 7.65 (1H, d, J=8.55 Hz), 7.59 (1H, s), 7.29-7.36 (2H, m), 7.11-7.21 (3H, m), 4.87-4.88 (4H, m), 4.47 (1H, s), 3.91 (3H, s), 3.11-3.19 (1H, m), 2.99-3.08 (1H, m), 2.77 (1H, dddd, J=13.47, 8.96, 4.43, 4.27 Hz), 2.13 (1H, dq, J=8.89, 6.70 Hz).

Workup

  1. concentrationThe reaction mixture was then concentrated in vacuo
  2. additionMeOH was added to the residue which
  3. customresulted in a suspension
  4. filtrationThis was filtered
  5. customto give a solid which
  6. filtrationfiltered
  7. concentrationThe filtrate was then concentrated in vacuo

Sources & evidence

ORD record
ord-e122df28e0d14083af81d6243620b96d
Source dataset
uspto-grants-2014_01
Patent number
US08637525B2

Reaction notes

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