Cesium carbonate → (5R,7R)-4-(1'-benzyl-4-((tert-butoxycarbonylamino)methyl)spiro[indoline-3,3'-pyrrolidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate

HRID 529131Notes

Reaction equation

HRID 529131 reaction equation
[N+:1]([C:4]1[CH:23]=[CH:22][C:7]([C:8]([O:10][C@H:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19](Cl)[C:14]=3[C@H:13]([CH3:21])[CH2:12]2)=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH2:24]([N:31]1[CH2:35][CH2:34][C:33]2([C:43]3[C:38](=[CH:39][CH:40]=[CH:41][C:42]=3[CH2:44][NH:45][C:46](=[O:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49])[NH:37][CH2:36]2)[CH2:32]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[N+:1]([C:4]1[CH:23]=[CH:22][C:7]([C:8]([O:10][C@H:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([N:37]4[C:38]5[C:43](=[C:42]([CH2:44][NH:45][C:46]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:52])[CH:41]=[CH:40][CH:39]=5)[C:33]5([CH2:34][CH2:35][N:31]([CH2:24][C:25]6[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=6)[CH2:32]5)[CH2:36]4)[C:14]=3[C@H:13]([CH3:21])[CH2:12]2)=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86651804(5R,7R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoateHCID 86651810Tert-butyl (1'-benzylspiro[indoline-3,3'-pyrrolidine]-4-yl)methylcarbamate

Product 1

HCID 68759216(5R,7R)-4-(1'-benzyl-4-((tert-butoxycarbonylamino)methyl)spiro[indoline-3,3'-pyrrolidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoateYield 79,090.898%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of (5R,7R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate (0.110 g, 0.330 mmol), tert-butyl (1′-benzylspiro[indoline-3,3′-pyrrolidine]-4-yl)methylcarbamate (0.130 g, 0.330 mmol), Cs2CO3 (0.162 g, 0.496 mmol), and Xantphos (28.7 mg, 0.050 mmol) in toluene (2.00 mL) was degassed by bubbling a stream of nitrogen through the solution. Pd(OAc)2 (7.42 mg, 0.0330 mmol) was then added to this solution, and the resulting mixture was heated overnight at 100° C. The reaction mixture was concentrated and purified by Analogix chromatography (DCM/5% MeOH/1% NH4OH) to give (5R,7R)-4-(1′-benzyl-4-((tert-butoxycarbonylamino)methyl)spiro[indoline-3,3′-pyrrolidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate (180 mg, 261 mmol, 79%). LCMS (APCI+) M+H+ 692 (100%); Rt=4.89 min.

Workup

  1. customby bubbling a stream of nitrogen through the solution
  2. concentrationThe reaction mixture was concentrated
  3. custompurified by Analogix chromatography (DCM/5% MeOH/1% NH4OH)

Sources & evidence

ORD record
ord-776db50c357e4e8b952cac979b17e6be
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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