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Diisopropylethylamine → 2-(1H-Benzo[d]imidazol-1-yl)-N-((R)-8-fluorochroman-4-yl)-5-nitropyrimidin-4-amine

HRID 1363134
Notes
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Reaction equation

HRID 1363134 reaction equation
F[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1OCC[C@H]2N.Cl[C:14]1[N:19]=C(Cl)C([N+]([O-])=O)=C[N:15]=1.CCN(C(C)C)C(C)C.Cl[C:34]1[N:39]=[C:38]([NH:40][C@H:41]2[C:50]3[C:45](=[C:46]([F:51])[CH:47]=[CH:48][CH:49]=3)[O:44][CH2:43][CH2:42]2)[C:37]([N+:52]([O-:54])=[O:53])=[CH:36][N:35]=1>C1COCC1>[N:15]1([C:34]2[N:39]=[C:38]([NH:40][C@H:41]3[C:50]4[C:45](=[C:46]([F:51])[CH:47]=[CH:48][CH:49]=4)[O:44][CH2:43][CH2:42]3)[C:37]([N+:52]([O-:54])=[O:53])=[CH:36][N:35]=2)[C:6]2[CH:5]=[CH:4][CH:3]=[CH:2][C:11]=2[N:19]=[CH:14]1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 5212662,4-Dichloro-5-nitropyrimidineHCID 46911919(R)-8-fluorochroman-4-amineHCID 59704905(R)-2-chloro-N-(8-fluorochroman-4-yl)-5-nitropyrimidin-4-amine

Product 1

HCID 597049352-(1H-Benzo[d]imidazol-1-yl)-N-((R)-8-fluorochroman-4-yl)-5-nitropyrimidin-4-amine

Reagents, catalysts & solvents

1
HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

(R)-8-fluorochroman-4-amine (60 mg, Example 29) was added to a solution of 2,4-dichloro-5-nitropyrimidine (70 mg) and DIEA (0.14 mL) in THF (5 mL) at −78° C. The reaction mixture was stirred for a further 15 min at −78° C. then removed from the cold bath and allowed to warm to RT. A one molar solution of the sodium salt of benzimidazole (0.7 ml, stock solution prepared via the addition of sodium hydride to a benzimidazole solution in THF) was added to the reaction intermediate ((R)-2-chloro-N-(8-fluorochroman-4-yl)-5-nitropyrimidin-4-amine) and the resulting mixture was stirred at RT overnight. Purification via column chromatography (elution with 1 MeOH/DCM) gave the titled compound (120 mg), MH+=407.

Workup

  1. customthen removed from the cold bath
  2. temperatureto warm to RT
  3. customA one molar solution of the sodium salt of benzimidazole (0.7 ml, stock solution prepared via the addition of sodium hydride to a benzimidazole solution in THF)
  4. stirringthe resulting mixture was stirred at RT overnight
  5. customPurification
  6. washvia column chromatography (elution with 1 MeOH/DCM)

Sources & evidence

ORD record
ord-2e1923ff88af41a9beac9615a5acfd41
Source dataset
uspto-grants-2011_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07884109B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes