1,1'-Carbonyldiimidazole → HCID 60198533, compound

HRID 2279507Notes

Reaction equation

HRID 2279507 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:12][C:13]([N:15]2[CH2:24][C:23]([F:26])([F:25])[C:22]3[CH:21]=[N:20][C:19]([NH:27][CH:28]4[CH2:33][CH2:32][O:31][CH2:30][CH2:29]4)=[N:18][C:17]=3[CH2:16]2)=[O:14])[CH2:9]OC)=[CH:4][C:3]=1F.[Cl:35]C1C=CC([C@H](N)COC)=CC=1F.C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.FC1(F)C2C=NC(NC3CCOCC3)=NC=2CNC1>O.C(Cl)Cl>[Cl:35][C:3]1[CH:4]=[C:5]([C@H:8]([NH:12][C:13]([N:15]2[CH2:24][C:23]([F:25])([F:26])[C:22]3[CH:21]=[N:20][C:19]([NH:27][CH:28]4[CH2:29][CH2:30][O:31][CH2:32][CH2:33]4)=[N:18][C:17]=3[CH2:16]2)=[O:14])[CH3:9])[CH:6]=[CH:7][C:2]=1[Cl:1]

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 86705500HCID 86705500, compoundHCID 86705502HCID 86705502, compoundHCID 86705503HCID 86705503, compound

Product 1

HCID 60198533HCID 60198533, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

(S)—N-(1-(4-chloro-3-fluorophenyl)-2-methoxyethyl)-5,5-difluoro-2-(tetrahydro-2H-pyran-4-ylamino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide (I-51) To a solution of 197 (0.0854 g, 0.293 mmol) and DCM (5 mL) was added sequentially TEA (0.123 mL, 0.880 mmol) and CDI (0.0476 g, 0.293 mmol) and the solution was stirred at RT for 30 min. To the solution was added dropwise a solution of TEA (0.123 mL, 0.880 mmol), 208 (0.090 g, 0.293 mmol) and DCM (5 mL). The reaction was stirred for 18 h then poured into water and extracted with DCM. The combined organic extracts were dried (MgSO4), filtered, and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with 2% MeOH/DCM to afford 0.060 g (40.9%) of I-51: MS m/z (APCI-pos) M+1=499.

Workup

  1. stirringThe reaction was stirred for 18 h
  2. extractionextracted with DCM
  3. dry with materialThe combined organic extracts were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by SiO2 chromatography
  7. washeluting with 2% MeOH/DCM
  8. customto afford 0.060 g (40.9%) of I-51

Sources & evidence

ORD record
ord-7c1eb5642099408dbe4e86aed027ccf2
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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