1,1'-Carbonyldiimidazole → N-{(6S,9R)-6-(2,3-Difluorophenyl)-3-[1-(trifluoromethyl)cyclopropyl]-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-9-yl}-4-(3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide

HRID 1664931Notes

Reaction equation

HRID 1664931 reaction equation
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[F:13][C:14]1[C:19]([F:20])=[CH:18][CH:17]=[CH:16][C:15]=1[C@H:21]1[CH2:27][N:26]2[C:28]([C:31]3([C:34]([F:37])([F:36])[F:35])[CH2:33][CH2:32]3)=[N:29][N:30]=[C:25]2[C@H:24]([NH2:38])[CH2:23][CH2:22]1.[CH3:39][N:40]1[C:44]2=[N:45][CH:46]=[CH:47][CH:48]=[C:43]2[N:42]([CH:49]2[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]2)[C:41]1=[O:55]>O1CCCC1>[F:13][C:14]1[C:19]([F:20])=[CH:18][CH:17]=[CH:16][C:15]=1[C@H:21]1[CH2:27][N:26]2[C:28]([C:31]3([C:34]([F:37])([F:35])[F:36])[CH2:32][CH2:33]3)=[N:29][N:30]=[C:25]2[C@H:24]([NH:38][C:1]([N:52]2[CH2:53][CH2:54][CH:49]([N:42]3[C:43]4[C:44](=[N:45][CH:46]=[CH:47][CH:48]=4)[N:40]([CH3:39])[C:41]3=[O:55])[CH2:50][CH2:51]2)=[O:2])[CH2:23][CH2:22]1

Participants

5

Reactant 3

HCID 682631,1'-Carbonyldiimidazole2×HCID 595851843-methyl-1-piperidin-4-yl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one2×HCID 67438617HCID 67438617, compound

Product 1

HCID 59722555N-{(6S,9R)-6-(2,3-Difluorophenyl)-3-[1-(trifluoromethyl)cyclopropyl]-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-9-yl}-4-(3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamideYield 69.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

1,1′-Carbonyldiimidazole (24.0 mg, 0.15 mmol) was added to a solution of (6S,9R)-6-(2,3-difluorophenyl)-3-[1-(trifluoromethyl)cyclopropyl]-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-9-amine (28 mg, 0.075 mmol) and in tetrahydrofuran (1.0 mL) at 0° C. After 30 min, additional 1,1′-carbonyldiimidazole (11.0 mg, 0.068 mmol) was added. After 30 min, 3-methyl-1-piperidin-4-yl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (26 mg, 0.113 mmol) was added and the mixture was heated to 60° C. After 1 h, additional 3-methyl-1-piperidin-4-yl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (23 mg, 0.099 mmol) was added. After 1 h, the reaction mixture was concentrated. Purification by reverse phase HPLC (100% water→100% acetonitrile with 0.1% trifluoroacetic acid) gave the title compound (33 mg). MS 631.2566 (M+1).

Workup

  1. waitAfter 30 min
  2. waitAfter 1 h
  3. waitAfter 1 h
  4. concentrationthe reaction mixture was concentrated
  5. customPurification by reverse phase HPLC (100% water→100% acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-bab8557620564692a412c03013399aa7
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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