Sodium Carbonate → tert-butyl (5-(3-(1-(3-fluorobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-3-methoxypyridin-2-yl)carbamate

HRID 531870Notes

Reaction equation

HRID 531870 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]3[CH:12]=[C:13]([O:25][CH3:26])[C:14]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[N:15][CH:16]=3)[CH:9]=2)[N:4]([S:27]([C:30]2[CH:36]=[CH:35][C:33]([CH3:34])=[CH:32][CH:31]=2)(=[O:29])=[O:28])[CH:3]=1.[F:37][C:38]1[CH:39]=[C:40]([CH:58]=[CH:59][CH:60]=1)[CH2:41][N:42]1[C:46]([CH3:47])=[C:45](B2OC(C)(C)C(C)(C)O2)[C:44]([CH3:57])=[N:43]1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.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]>[F:37][C:38]1[CH:39]=[C:40]([CH:58]=[CH:59][CH:60]=1)[CH2:41][N:42]1[C:46]([CH3:47])=[C:45]([C:2]2[C:10]3[C:5](=[N:6][CH:7]=[C:8]([C:11]4[CH:12]=[C:13]([O:25][CH3:26])[C:14]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[N:15][CH:16]=4)[CH:9]=3)[N:4]([S:27]([C:30]3[CH:36]=[CH:35][C:33]([CH3:34])=[CH:32][CH:31]=3)(=[O:29])=[O:28])[CH:3]=2)[C:44]([CH3:57])=[N:43]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 900306711-(3-Fluoro-benzyl)-3,5-dimethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole2×HCID 90064827tert-butyl (5-(3-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-3-methoxypyridin-2-yl)carbamate2×

Product 1

HCID 131735682tert-butyl (5-(3-(1-(3-fluorobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-3-methoxypyridin-2-yl)carbamateYield 89.2%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 86587398Ethanol toluene waterSolvent

Procedure

Using similar reaction conditions as described in step-i of example-1, tert-butyl (5-(3-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-3-methoxypyridin-2-yl)carbamate (intermediate 66B) (200 mg, 0.322 mmol) was coupled with 1-(3-fluorobenzyl)-3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (intermediate 16) (160 mg, 0.483 mmol) using Pd(dppf)Cl2 (12 mg, 0.016 mol) and sodium carbonate (103 mg, 0.967 mmol) in toluene/ethanol/water (5/2/1 ml) to afford 200 mg (89.2% yield) of the titled compound after column purification using 2% methanol in DCM as eluent. MS: m/z=597.5 (M-Boc+1).

Workup

  1. customreaction conditions

Sources & evidence

ORD record
ord-21857b48eb614041b32d7d695490ee1f
Source dataset
uspto-grants-2016_05
Patent number
US09353107B2

Reaction notes

Loading…