Dichloromethane → tert-butyl 5-(2-(3-((R)-1-(2,2,2-trifluoroacetyl)pyrrolidine-2-carboxamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate

HRID 1808403Notes

Reaction equation

HRID 1808403 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[N:17]=[C:16]([NH:18][C:19]3[CH:20]=[C:21]4[C:25](=[CH:26][CH:27]=3)[N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[N:23]=[CH:22]4)[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[F:35][C:36]([F:48])([F:47])[C:37]([N:39]1[CH2:43][CH2:42][CH2:41][CH:40]1[C:44](Cl)=[O:45])=[O:38].C(Cl)Cl>CN(C1C=CN=CC=1)C.CCN(CC)CC>[F:48][C:36]([F:35])([F:47])[C:37]([N:39]1[CH2:43][CH2:42][CH2:41][C@@H:40]1[C:44]([NH:1][C:2]1[CH:3]=[C:4]([C:8]2[N:17]=[C:16]([NH:18][C:19]3[CH:20]=[C:21]4[C:25](=[CH:26][CH:27]=3)[N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[N:23]=[CH:22]4)[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1)=[O:45])=[O:38]

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 33893892-Pyrrolidinecarbonyl chloride, 1-(trifluoroacetyl)-2×HCID 66825994tert-butyl 5-(2-(3-aminophenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate

Product 1

HCID 59361903tert-butyl 5-(2-(3-((R)-1-(2,2,2-trifluoroacetyl)pyrrolidine-2-carboxamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8471TriethylamineSolvent2×

Procedure

To a suspension of tert-butyl 5-(2-(3-aminophenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate (20 mg, 0.044 mmol) and 1-(2,2,2-trifluoroacetyl)pyrrolidine-2-carbonyl chloride (880 μL, 0.088 mmol, 0.1M solution in CH2Cl2) was added Et3N (12 μL, 0.088 mmol), catalytic amount of DMAP, and CH2Cl2 (1 mL). The reaction mixture was stirred at RT for 2 h after which 2 equivalents each of 1-(2,2,2-trifluoroacetyl)pyrrolidine-2-carbonyl chloride and Et3N were added. Continued to stir at ambient temperature for 16 hours. The reaction was concentrated in vacuo and the residue was purified by flash chromatography on silica (10:1 CH2Cl2:MeOH). The product tert-butyl 5-(2-(3-((R)-1-(2,2,2-trifluoroacetyl)pyrrolidine-2-carboxamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate was isolated. (130 mg, 46%)

Workup

  1. additionwere added
  2. concentrationThe reaction was concentrated in vacuo
  3. customthe residue was purified by flash chromatography on silica (10:1 CH2Cl2:MeOH)

Sources & evidence

ORD record
ord-3abf4b19d8734cbbb2bcf067804c7a05
Source dataset
uspto-grants-2013_01
Patent number
US08357693B2

Reaction notes

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