2-Chloropyrimidine → HCID 57833355, compound

HRID 729972Notes

Reaction equation

HRID 729972 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([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:3]=1.ClC1N=CC=CN=1.Br[C:37]1[CH:42]=[CH:41][N:40]=[C:39]([O:43][C:44]2C=CC(NC3N=C(N)C=C(C4C=CC=CC=4)N=3)=CC=2)[CH:38]=1.COC[C@@H]1CCCN1>>[CH3:44][O:43][CH2:39][C@@H:38]1[CH2:37][CH2:42][CH2:41][N:40]1[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([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:3]=1

Participants

5

Reactant 4

HCID 744042-ChloropyrimidineHCID 671217(S)-(+)-2-(Methoxymethyl)pyrrolidineHCID 57833345HCID 57833345, compoundHCID 68517957HCID 68517957, compound

Product 1

HCID 57833355HCID 57833355, compoundYield 40%

Conditions

Temperature
108 °C

Procedure

N4-{4-[(4-Bromopyridin-2-yl)oxy]phenyl}-6-phenylpyrimidine-2,4-diamine (75 mg, 0.17 mmol, was prepared by the method of Example 1 using and Intermediates 2T and 1A as starting materials. N-[4-(4-bromo-pyridin-2-yloxy)-phenyl]-6-phenyl-pyrimidine-2,4-diamine, was then combined with (S)-(+)-2-(methoxymethyl)pyrrolidine (99.5 mg, 0.86 mmol) in a 5-mL reaction flask and heated at 108° C. with stirring for 24 h. TLC and LC-MS indicated that the reaction was complete. After cooling to rt, the reaction mixture was extracted with EtOAc and washed with 1N aqueous sodium hydroxide solution (2×) and H2O (3×). The organic layer was dried and concentrated to give 75 mg of the crude product. The residue was purified by Prep-TLC (CH3OH:EtOAc=2:8) to obtain 32 mg (40%) of the title product as a yellowish oil. 1H NMR (CD3OD) δ 7.82 (m, 2H), 7.70 (m, 3H), 7.41 (m, 3H), 7.04 (d, 2H), 6.41 (m, 2H), 5.94 (s, 1H), 3.86 (s, 1H), 3.38 (m, 2H), 3.30 (m, 3H), 3.18 (m, 1H), 2.01 (m, 4H), 1.30 (m, 1H); MS ES 469 (M+H)+, calcd 469, RT=1.9 min; TLC (EtOAc) Rf=0.2.

Workup

  1. temperatureAfter cooling to rt
  2. extractionthe reaction mixture was extracted with EtOAc
  3. washwashed with 1N aqueous sodium hydroxide solution (2×) and H2O (3×)
  4. customThe organic layer was dried
  5. concentrationconcentrated
  6. customto give 75 mg of the crude product
  7. customThe residue was purified by Prep-TLC (CH3OH:EtOAc=2:8)

Sources & evidence

ORD record
ord-01bddf0e4c7543ae8b21db5de3b4d083
Source dataset
uspto-grants-2009_09
Patent number
US07582646B2

Reaction notes

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