Bromo tert-butylacetate → {4-[1-(3-trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-5,8-dihydro-6H-pyrido[3,4-d]pyrimidin-7-yl}-acetic acid tert-butyl ester

HRID 45073Notes

Reaction equation

HRID 45073 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([NH:9][C:10]([N:12]2[C:20]3[C:15](=[CH:16][C:17]([O:21][C:22]4[C:23]5[CH2:31][CH2:30][NH:29][CH2:28][C:24]=5[N:25]=[CH:26][N:27]=4)=[CH:18][CH:19]=3)[CH:14]=[CH:13]2)=[O:11])[CH:6]=[CH:7][CH:8]=1.C([CH2:38][C:39]([O:41]Br)=[O:40])(C)(C)C>C(#N)C>[C:3]([O:41][C:39](=[O:40])[CH2:38][N:29]1[CH2:30][CH2:31][C:23]2[C:22]([O:21][C:17]3[CH:16]=[C:15]4[C:20](=[CH:19][CH:18]=3)[N:12]([C:10](=[O:11])[NH:9][C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:1])([F:32])[F:33])[CH:4]=3)[CH:13]=[CH:14]4)=[N:27][CH:26]=[N:25][C:24]=2[CH2:28]1)([CH3:4])([CH3:8])[CH3:2]

Participants

4

Reactant 2

HCID 22013197Bromo tert-butylacetateHCID 462242625-(5,6,7,8-Tetrahydro-pyrido[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

Product 1

HCID 59394435{4-[1-(3-trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-5,8-dihydro-6H-pyrido[3,4-d]pyrimidin-7-yl}-acetic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 5-(5,6,7,8-tetrahydro-pyrido[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide, Example 33-C, (250 mg, 0.55 mmol), bromo tert-butylacetate (204 μL, 1.38 mmol), TEA (384 μL, 2.76 mmol) and ACN (5 mL) is stirred at room temperature. Following completion of the reaction the contents of the flask are partitioned between DCM and brine. Organic layer is dried over anhydrous Na2SO4, concentrated, and the residue is separated via FCC (50-100% EtOAc/heptane) to give the title compound. MS (ESI) m/z 568.1 (M+1).

Workup

  1. customcompletion of the reaction the contents of the flask
  2. customare partitioned between DCM and brine
  3. dry with materialOrganic layer is dried over anhydrous Na2SO4
  4. concentrationconcentrated
  5. customthe residue is separated via FCC (50-100% EtOAc/heptane)

Sources & evidence

ORD record
ord-03202f1d9ca342bbb0c29f2a0dd307b8
Source dataset
uspto-grants-2013_09
Patent number
US08541432B2

Reaction notes

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