4-Methylmorpholine → 3-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentyl N-(2-morpholinoethyl)carbamate

HRID 51542Notes

Reaction equation

HRID 51542 reaction equation
CN1CC[O:5][CH2:4]C1.[NH2:8][C:9]1[C:10]2[C:17]([C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[CH:20][CH:19]=3)=[CH:16][N:15]([CH:31]3[CH2:35][CH2:34][CH:33]([OH:36])[CH2:32]3)[C:11]=2[N:12]=[CH:13][N:14]=1.[O:37]1[CH2:42][CH2:41][N:40]([CH2:43][CH2:44][NH2:45])[CH2:39][CH2:38]1>ClCCl.C(OCC)(=O)C>[O:37]1[CH2:42][CH2:41][N:40]([CH2:43][CH2:44][NH:45][C:4](=[O:5])[O:36][CH:33]2[CH2:34][CH2:35][CH:31]([N:15]3[C:11]4[N:12]=[CH:13][N:14]=[C:9]([NH2:8])[C:10]=4[C:17]([C:18]4[CH:19]=[CH:20][C:21]([O:24][C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)=[CH:22][CH:23]=4)=[CH:16]3)[CH2:32]2)[CH2:39][CH2:38]1

Participants

6

Reactant 3

HCID 79724-MethylmorpholineHCID 4082852-MorpholinoethylamineHCID 227362353-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentan-1-ol

Product 1

HCID 227362693-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentyl N-(2-morpholinoethyl)carbamate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

4- Nitrochloroformate (12.5 mg, 0.062 mmol) in dichloromethane (1 mL) was cooled on an ice-water bath. 4-Methylmorpholine (7 uL, 0.062 mmol) was added slowly. After 20 minutes, the ice-water bath was removed and the reaction mixture was allowed to warm up to room temperature. 3-(4-Amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-cyclopentanol (20 mg, 0.052 mmol) was added and the reaction mixture was stirred for 4days. The reaction mixture was diluted with dichloromethane. The organic layer was washed with water, saturated sodium bicarbonate, brine, dried over MgSO4, filtered and evaporated to give a yellow solid. A solution of the yellow solid in dichloromethane (1 mL) was added to 2-morpholino-1-ethanamine (0.2 mL). After stirring at room temperature overnight, the reaction mixture was diluted with ethyl acetate. The organic layer was washed with water (3 times), brine, dried over MgSO4, filtered and evaporated. The crude product was purified by HPLC to give 3-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentyl N-(2-morpholinoethyl)carbamate (17 mg, 0.031 mmol). 1H NMR (CDCl3-d) δ 2.08 (m, 4H), 2.43 (m, 7H), 2.73 (m, 1H), 3.29 (m, 2H), 3.67, (m, 4H), 5.28 (m, 5H), 7.09 (m, 6H), 7.40 (m, 4H), 8.30 (s, 1H). LC/MS: MH+=543, tr=2.13 min. (Pecospher, 3C-18, 3 um, 4.6×33 mm; 0-100% acetonitrile—0.1 M ammonium acetate over 5 min, 3.5 ml/min).

Workup

  1. customthe ice-water bath was removed
  2. washThe organic layer was washed with water, saturated sodium bicarbonate, brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customto give a yellow solid
  7. stirringAfter stirring at room temperature overnight
  8. washThe organic layer was washed with water (3 times), brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. customevaporated
  12. customThe crude product was purified by HPLC

Sources & evidence

ORD record
ord-b5bba0d402e44f72b4b4b794e45394ab
Source dataset
uspto-grants-2004_03
Patent number
US06713474B2

Reaction notes

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