Water → HCID 66612003, compound

HRID 1812093Notes

Reaction equation

HRID 1812093 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([N:16]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)[CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=3)[N:10]=2)[C:5](F)=[N:6][CH:7]=1.[NH2:35][C:36]1[CH:37]=[CH:38][C:39]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[N:40][CH:41]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.O>C1COCC1>[CH3:25][O:24][C:21]1[CH:22]=[CH:23][C:18]([CH2:17][N:16]([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[C:11]2[N:12]=[C:13]([CH3:15])[N:14]=[C:9]([C:4]3[C:5]([NH:35][C:36]4[CH:37]=[CH:38][C:39]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:47])([CH3:46])[CH3:48])=[N:40][CH:41]=4)=[N:6][CH:7]=[C:2]([Cl:1])[CH:3]=3)[N:10]=2)=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 962WaterHCID 2733832Lithium HexamethyldisilazideHCID 22064440tert-butyl N-(5-aminopyridin-2-yl)carbamateHCID 666005044-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 66612003HCID 66612003, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 4-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.723 g, 1.51 mmol) and tert-butyl 5-aminopyridin-2-ylcarbamate (Example 190, Step 2, 0.317 g, 1.52 mmol) in THF (5 mL) was treated dropwise with LiHMDS (4.52 mL, 4.52 mmol) at 0° C. The dark red mixture was stirred at 0° C. for 30 min. Water (0.2 mL) was added to quench the reaction. The reaction mixture was partitioned between saturated aqueous ammonium chloride (40 mL) and EtOAc (40 mL). The aqueous phase was extracted with EtOAc (20 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (50 g, eluent: EtOAc in hexanes 0%-35%) to give tert-butyl 5-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-chloropyridin-2-ylamino)pyridin-2-ylcarbamate (0.697 g, 69% yield) as a yellow foam. 1H NMR (300 MHz, CDCl3) δ 11.77 (s, 1H); 8.74 (d, J=2.34 Hz, 1H); 8.39 (br. s., 1H); 8.22 (s, 1H); 7.79-7.94 (m, 2H); 7.28 (br. s., 1H); 7.19 (t, J=9.28 Hz, 4H); 6.86 (dd, J=8.18, 3.95 Hz, 4H); 4.83 (d, J=11.55 Hz, 4H); 3.80 (d, J=4.97 Hz, 6H); 2.58 (s, 3H); 1.53 (s, 9H). m/z (ESI, +ve ion) 669.2 (M+H)+.

Workup

  1. customto quench
  2. customthe reaction
  3. customThe reaction mixture was partitioned between saturated aqueous ammonium chloride (40 mL) and EtOAc (40 mL)
  4. extractionThe aqueous phase was extracted with EtOAc (20 mL)
  5. dry with materialThe combined organic phases were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by column chromatography (50 g, eluent: EtOAc in hexanes 0%-35%)

Sources & evidence

ORD record
ord-8b420d2cf3124708a67fb9888e250305
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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