1,1'-Carbonyldiimidazole → 2-(tetrahydro-pyran-4-ylamino)-5,8-dihydro-6H-pyrido[3,4-d]pyrimidine-7-carboxylic acid [4-(4-chloro-3-fluoro-phenoxy)-1-methyl-pyrrolidin-3-yl]-amide

HRID 2279606Notes

Reaction equation

HRID 2279606 reaction equation
[Cl:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C@@H:7]2[CH2:11][N:10]([CH3:12])[CH2:9][C@H:8]2[NH2:13])=[CH:4][C:3]=1[F:16].C1N=CN([C:22](N2C=NC=C2)=[O:23])C=1.[O:29]1[CH2:34][CH2:33][CH:32]([NH:35][C:36]2[N:37]=[CH:38][C:39]3[CH2:45][CH2:44][NH:43][CH2:42][C:40]=3[N:41]=2)[CH2:31][CH2:30]1>C(Cl)Cl>[Cl:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][CH:7]2[CH2:11][N:10]([CH3:12])[CH2:9][CH:8]2[NH:13][C:22]([N:43]2[CH2:44][CH2:45][C:39]3[CH:38]=[N:37][C:36]([NH:35][CH:32]4[CH2:31][CH2:30][O:29][CH2:34][CH2:33]4)=[N:41][C:40]=3[CH2:42]2)=[O:23])=[CH:4][C:3]=1[F:16]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 71743546N-(tetrahydro-2H-pyran-4-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-amineHCID 86705587trans-(+/-)-4-(4-Chloro-3-fluorophenoxy)-1-methylpyrrolidin-3-amine

Product 1

HCID 601989662-(tetrahydro-pyran-4-ylamino)-5,8-dihydro-6H-pyrido[3,4-d]pyrimidine-7-carboxylic acid [4-(4-chloro-3-fluoro-phenoxy)-1-methyl-pyrrolidin-3-yl]-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 428 (0.085 g, 0.347 mmol) and DCM (15 mL) was added TEA (1 mL) and CDI (0.149 g, 0.919 mmol). The mixture was stirred at RT for 1 h and then 28 (0.081 g, 0.35 mmol) was added. The reaction was stirred at RT for 2 h. The solvent was removed in vacuo and the residue was purified by preparative reverse HPLC to afford 31 mg (28%) of I-151 as a white solid: LC-MS (ESI) m/z 505 (M+H).

Workup

  1. stirringThe reaction was stirred at RT for 2 h
  2. customThe solvent was removed in vacuo
  3. customthe residue was purified by preparative reverse HPLC
  4. customto afford 31 mg (28%) of I-151 as a white solid

Sources & evidence

ORD record
ord-c8109e521ca540198329c4d439437e6f
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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