Imidazole → (S)-1-((1-hydroxycyclobutyl)(phenyl)methyl)-3-(3-(2-methoxyethoxy)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea

HRID 588199Notes

Reaction equation

HRID 588199 reaction equation
C1N=CN([C:6](N2C=NC=C2)=[O:7])C=1.[CH3:13][O:14][CH2:15][CH2:16][O:17][C:18]1[C:22]2[CH:23]=[N:24][C:25]([NH2:27])=[CH:26][C:21]=2[N:20]([C:28]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:19]=1.N1C=CN=C1.[NH2:52][C@@H:53]([C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)[C:54]1([OH:58])[CH2:57][CH2:56][CH2:55]1>O1CCCC1>[OH:58][C:54]1([C@H:53]([C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[NH:52][C:6]([NH:27][C:25]2[N:24]=[CH:23][C:22]3[C:18]([O:17][CH2:16][CH2:15][O:14][CH3:13])=[N:19][N:20]([C:28]([C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)([C:35]4[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=4)[C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[C:21]=3[CH:26]=2)=[O:7])[CH2:55][CH2:56][CH2:57]1

Participants

6

Reactant 4

HCID 795ImidazoleHCID 682631,1'-CarbonyldiimidazoleHCID 86334021(S)-1-(amino(phenyl)methyl)cyclobutanolHCID 1182720223-(2-methoxyethoxy)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-amine

Product 1

HCID 118271731(S)-1-((1-hydroxycyclobutyl)(phenyl)methyl)-3-(3-(2-methoxyethoxy)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)ureaYield 74.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

CDI (36.0 mg, 0.222 mmol) was added to a stirred, room temperature mixture of 3-(2-methoxyethoxy)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-amine 32B (50 mg, 0.111 mmol) and imidazole (30.2 mg, 0.444 mmol) in tetrahydrofuran (1 mL), and the mixture was stirred at room temperature for overnight. The mixture turned from light yellow slurry to clear solution. (S)-1-(amino(phenyl)methyl)cyclobutanol (19.67 mg, 0.111 mmol) was added to mixture and the resultant mixture was kept stirring at room temperature for overnight. The residue was purified (24 g silica, eluting with 50% EtOAc/isohexane) to give (S)-1-((1-hydroxycyclobutyl)(phenyl)methyl)-3-(3-(2-methoxyethoxy)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea (54 mg, 74% yield) as a white solid. MS: [M+H]+ m/z 654.

Workup

  1. customThe residue was purified
  2. wash(24 g silica, eluting with 50% EtOAc/isohexane)

Sources & evidence

ORD record
ord-ed62220b6c1445a5b0692b6845cc0764
Source dataset
uspto-grants-2016_01
Patent number
US09226922B2

Reaction notes

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