(S)-(+)-2-(Methoxymethyl)pyrrolidine → HCID 57833416, compound

HRID 729922Notes

Reaction equation

HRID 729922 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[CH:21]=[C:20]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[N:19]=[C:18]([NH2:28])[N:17]=3)=[CH:11][CH:10]=2)[CH:5]=[CH:4][N:3]=1.[CH3:29][O:30][CH2:31][C@@H:32]1[CH2:36][CH2:35][CH2:34][NH:33]1>>[CH3:29][O:30][CH2:31][C@@H:32]1[CH2:36][CH2:35][CH2:34][N:33]1[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([NH:15][C:16]3[CH:21]=[C:20]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[N:19]=[C:18]([NH2:28])[N:17]=3)=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1

Participants

3

Reactant 2

HCID 671217(S)-(+)-2-(Methoxymethyl)pyrrolidineHCID 57833225HCID 57833225, compound

Product 1

HCID 57833416HCID 57833416, compound

Conditions

Temperature
80 °C

Procedure

A mixture of N4-{4-[(2-chloropyridin-4-yl)oxy]phenyl}-6-phenylpyrimidine-2,4-diamine (0.15 g, 0.38 mmol, prepared in Example 48) and (S)-(+)-2-(methoxymethyl)pyrrolidine (2 mL) was heated at 80° C. for 3 days. The mixture was cooled to rt and separated by preparative HPLC directly. The desired fractions were combined, neutralized by 10% sodium carbonate, and extracted with EtOAc (3×). The extracts were combined, dried over magnesium sulfate, and evaporated to furnish pure product, 0.04 g (22%). 1H NMR (DMSO-d6) δ 9.24 (s, 1H), 7.89 (m, 3H), 7.78 (m, 2H), 7.42 (m, 3H), 7.00 (m, 2H), 6.44 (s, 1H), 6.34 (s, 2H), 6.10 (m, 1H), 5.85 (d, 1H), 4.06 (m, 2H), 3.40 (m, 1H), 3.21 (s, 3H), 3.08 (m, 4H), 1.82 (m, 4H); MS ES 469 (M+H)+ calc 469.

Workup

  1. temperatureThe mixture was cooled to rt
  2. customseparated by preparative HPLC directly
  3. extractionextracted with EtOAc (3×)
  4. dry with materialdried over magnesium sulfate
  5. customevaporated
  6. customto furnish pure product, 0.04 g (22%)

Sources & evidence

ORD record
ord-9ededb3446cf48868c972d437b3c686e
Source dataset
uspto-grants-2009_09
Patent number
US07582645B2

Reaction notes

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