Diisopropylethylamine → 2-(5-Fluoro-4-methylpyrimidin-2-yl)-5-{[4-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}octahydropyrrolo[3,4-c]pyrrole

HRID 244051Notes

Reaction equation

HRID 244051 reaction equation
[CH2:1]1[CH:5]2[CH2:6][NH:7][CH2:8][CH:4]2[CH2:3][N:2]1[C:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][C:12]=1[N:19]1[N:23]=[CH:22][CH:21]=[N:20]1)=[O:10].Cl[C:25]1[N:30]=[C:29]([CH3:31])[C:28]([F:32])=[CH:27][N:26]=1.CCN(C(C)C)C(C)C>C(#N)C>[F:32][C:28]1[C:29]([CH3:31])=[N:30][C:25]([N:7]2[CH2:8][CH:4]3[CH:5]([CH2:1][N:2]([C:9]([C:11]4[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][C:12]=4[N:19]4[N:20]=[CH:21][CH:22]=[N:23]4)=[O:10])[CH2:3]3)[CH2:6]2)=[N:26][CH:27]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 207780732-Chloro-5-fluoro-4-methylpyrimidine2×HCID 67116159(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)(4-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone

Product 1

HCID 671167092-(5-Fluoro-4-methylpyrimidin-2-yl)-5-{[4-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}octahydropyrrolo[3,4-c]pyrrole

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

(Hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)(4-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone (Example 288—step B, 33 mg, 0.10 mmol), 2-chloro-5-fluoro-4-methylpyrimidine (Intermediate 55, 15 mg, 0.10 mmol) and DIPEA (54 μL, 0.3 mmol) in ACN (1 mL) were heated in a microwave reactor for 2 h at 200° C. Then the reaction mixture was concentrated and purified via prep HPLC (Agilent, basic) gave the title compound as a clear oil. MS (ESI) mass calcd. C21H22FN7O2, 423.45; m/z found 424.2 [M+H]+. 1H NMR (CDCl3): 8.06 (d, J=1.8 Hz, 1H), 7.74 (s, 2H), 7.50 (d, J=5.8 Hz, 1H), 7.33 (d, J=8.5 Hz, 1H), 6.95 (dd, J=8.5, 2.5 Hz, 1H), 3.93-3.76 (m, 5H), 3.71-3.59 (m, 2H), 3.53 (dd, J=11.4, 5.2 Hz, 1H), 3.44-3.30 (m, 2H), 3.07-2.87 (m, 3H), 2.37 (t, J=4.9 Hz, 3H).

Workup

  1. customwere heated in a microwave reactor for 2 h at 200° C
  2. concentrationThen the reaction mixture was concentrated
  3. custompurified via prep HPLC (Agilent, basic)

Sources & evidence

ORD record
ord-33a7f62cd9ad4f2da91313fde708b8f6
Source dataset
uspto-grants-2014_02
Patent number
US08653263B2

Reaction notes

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