Sodium Carbonate → 2-((1S)-1-((6-amino-5-(4-(methylsulfonyl)phenyl)-4-pyrimidinyl)amino)ethyl)-1-cyclopropyl-N-methyl-1H-benzimidazole-7-carboxamide

HRID 2036579Notes

Reaction equation

HRID 2036579 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:11]2[N:15]([CH:16]3[CH2:18][CH2:17]3)[C:14]3[C:19]([C:23]([NH:25][CH3:26])=[O:24])=[CH:20][CH:21]=[CH:22][C:13]=3[N:12]=2)[CH3:10])[C:3]=1I.C([O-])([O-])=O.[Na+].[Na+].[CH3:34][S:35]([C:38]1[CH:43]=[CH:42][C:41](B(O)O)=[CH:40][CH:39]=1)(=[O:37])=[O:36]>COCCOC.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:11]2[N:15]([CH:16]3[CH2:18][CH2:17]3)[C:14]3[C:19]([C:23]([NH:25][CH3:26])=[O:24])=[CH:20][CH:21]=[CH:22][C:13]=3[N:12]=2)[CH3:10])[C:3]=1[C:41]1[CH:42]=[CH:43][C:38]([S:35]([CH3:34])(=[O:37])=[O:36])=[CH:39][CH:40]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27343644-(Methanesulfonyl)phenylboronic acidHCID 58459347(S)-2-(1-(6-amino-5-iodopyrimidin-4-ylamino)ethyl)-1-cyclopropyl-N-methyl-1H-benzo[d]imidazole-7-carboxamide

Product 1

HCID 534828152-((1S)-1-((6-amino-5-(4-(methylsulfonyl)phenyl)-4-pyrimidinyl)amino)ethyl)-1-cyclopropyl-N-methyl-1H-benzimidazole-7-carboxamide

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (S)-2-(1-(6-amino-5-iodopyrimidin-4-ylamino)ethyl)-1-cyclopropyl-N-methyl-1H-benzo[d]imidazole-7-carboxamide (Prepared in Example 20, 50.4 mg, 0.106 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (17.25 mg, 0.021 mmol), Na2CO3 (0.026 ml, 0.634 mmol), 4-(methanesulfonyl)-benzeneboronic acid (52.8 mg, 0.264 mmol) in anhydrous 1,2-dimethoxyethane (5 mL) and water (1 mL) was heated to 80° C. under N2. After 1 h, the mixture was cooled to rt and filtered. The filtrate was concentrated under reduced pressure, and purified by column chromatography on a silica gel column using 0 to 10% gradient of MeOH in DCM-EtOAc (1:1) as eluent to give 2-((1S)-1-((6-amino-5-(4-(methylsulfonyl)phenyl)-4-pyrimidinyl)amino)ethyl)-1-cyclopropyl-N-methyl-1H-benzimidazole-7-carboxamide: 1H NMR (400 MHz, DMSO-d6) δ 8.42-8.37 (m, 1H), 8.06 (d, J=8 Hz, 2H), 8.01 (s, 1H), 7.61 (d, J=8 Hz, 2H), 7.56 (d, J=8 Hz, 1H), 7.20 (d, J=8 Hz, 1H), 7.15 (dd, J=8, 8 Hz, 1H), 5.85-5.75 (m, 2H), 3.28 (s, 3H), 2.83 (d, J=4 Hz, 3H), 1.49 (d, J=8 Hz, 3H), 1.18-1.08 (m, 2H), 0.98-0.92 (m, 1H), 0.83-0.75 (m, 1H); LC-MS (ESI) m/z 506.0 [M+H]+.

Workup

  1. temperaturethe mixture was cooled to rt
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. custompurified by column chromatography on a silica gel column

Sources & evidence

ORD record
ord-63586a92634b4b30b84ab79178409abc
Source dataset
uspto-grants-2013_11
Patent number
US08575183B2

Reaction notes

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