Carbonic acid-guanidine (1:1) → 1-{1-[4-(2,4-diamino-6-phenylpyrido[2,3-d]pyrimidin-7-yl)benzyl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one

HRID 1354811Notes

Reaction equation

HRID 1354811 reaction equation
C(=O)(O)O.[NH2:5][C:6]([NH2:8])=[NH:7].CC(C)([O-])C.[K+].Cl[C:16]1[N:23]=[C:22]([C:24]2[CH:29]=[CH:28][C:27]([CH2:30][N:31]3[CH2:36][CH2:35][CH:34]([N:37]4[C:41]5[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=5[NH:39][C:38]4=[O:46])[CH2:33][CH2:32]3)=[CH:26][CH:25]=2)[C:21]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)=[CH:20][C:17]=1[C:18]#[N:19]>CC(N(C)C)=O>[NH2:7][C:6]1[N:8]=[C:18]([NH2:19])[C:17]2[CH:20]=[C:21]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)[C:22]([C:24]3[CH:29]=[CH:28][C:27]([CH2:30][N:31]4[CH2:36][CH2:35][CH:34]([N:37]5[C:41]6[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=6[NH:39][C:38]5=[O:46])[CH2:33][CH2:32]4)=[CH:26][CH:25]=3)=[N:23][C:16]=2[N:5]=1

Participants

5

Reactant 3

HCID 286947Carbonic acid-guanidine (1:1)HCID 114098042-Chloro-6-(4-{[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl]-5-phenylnicotinonitrileHCID 23665647Potassium tert-butoxide

Product 1

HCID 211031011-{1-[4-(2,4-diamino-6-phenylpyrido[2,3-d]pyrimidin-7-yl)benzyl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
50 °C

Procedure

Guanidine carbonate (0.036 g, 0.2 mmol) was added to a suspension of potassium tert-butoxide (0.045 g, 0.4 mmol) in dimethylacetamide (1.0 mL). The mixture was stirred at 50° C. for 10 min. Then 2-chloro-6-(4-{[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl)-5-phenylnicotinonitrile (11-5) (0.052 g, 0.1 mmol) was added. The mixture was then heated to 140° C. for 20 min in microwave. Purification directly with reverse phase HPLC (5–100% CH3CN/H2O+0.1% TFA) gave 1-{1-[4-(2,4-diamino-6-phenylpyrido[2,3-d]pyrimidin-7-yl)benzyl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one (11-6) as a off-white solid. 1H NMR (DMSO-d6) δ 8.59 (s, 1H), 8.45 (broad, 4H), 6.91–7.34 (m, 13H), 4.17–4.21(m, 1H), 3.60 (m, 4H), 3.34 (m, 2H), 2.38 (m, 2H), 2.12–2.23 (m, 2H). LRMS m/z (M+H) Calcd: 543.6, found: 543.2.

Workup

  1. temperatureThe mixture was then heated to 140° C. for 20 min in microwave
  2. customPurification directly with reverse phase HPLC (5–100% CH3CN/H2O+0.1% TFA)

Sources & evidence

ORD record
ord-363fedf41ab64a788ffd996936b86331
Source dataset
uspto-grants-2007_05
Patent number
US07223738B2

Reaction notes

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