Tetrahydrofuran → HCID 60198532, compound

HRID 2279504Notes

Reaction equation

HRID 2279504 reaction equation
[Si]([O:8][CH2:9][C@@H:10]([NH:19][C:20]([N:22]1[CH2:31][CH2:30][C:29]2[CH:28]=[N:27][C:26]([NH:32][CH:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[N:25][C:24]=2[CH2:23]1)=[O:21])[C:11]1[CH:16]=[CH:15][C:14]([F:17])=[C:13]([Cl:18])[CH:12]=1)(C(C)(C)C)(C)C.C1COCC1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>O>[Cl:18][C:13]1[CH:12]=[C:11]([C@H:10]([NH:19][C:20]([N:22]2[CH2:31][CH2:30][C:29]3[CH:28]=[N:27][C:26]([NH:32][CH:33]4[CH2:38][CH2:37][O:36][CH2:35][CH2:34]4)=[N:25][C:24]=3[CH2:23]2)=[O:21])[CH2:9][OH:8])[CH:16]=[CH:15][C:14]=1[F:17]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 2724141Tetrabutylammonium FluorideHCID 86705499HCID 86705499, compound

Product 1

HCID 60198532HCID 60198532, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of (S)—N-(2-(tert-butyldimethylsilyloxy)-1-(3-chloro-4-fluorophenyl)ethyl)-2-(tetrahydro-2H-pyran-4-ylamino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide (0.250 g, 0.443 mmol) and THF (5 mL) at RT was added TBAF (0.532 mL, 0.532 mmol) and the reaction was stirred for 1 h at RT, poured into water and extracted with DCM. The combined organic fractions were dried (MgSO4), filtered, and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with a DCM/MeOH gradient (500:20 to 500:30) to afford 0.100 g (50.2%) of I-46: 1H NMR (400 MHz, d6-DMSO) δ 8.08 (s, 1H), 7.52 (d, 1H), 7.32 (d, 2H), 6.91-6.86 (m, 2H), 4.85 (br s, 1H), 4.74 (m, 1H), 4.40-4.30 (m, 2H), 3.87-3.84 (m, 3H), 3.58-3.54 (m, 4H), 3.38-3.31 (m, 2H), 2.56-2.54 (m, 2H), 1.81-1.78 (m, 2H), 1.53-1.46 (m, 2H); MS m/z (APCI-pos) M+1=450.

Workup

  1. extractionextracted with DCM
  2. dry with materialThe combined organic fractions were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by SiO2 chromatography
  6. washeluting with a DCM/MeOH gradient (500:20 to 500:30)
  7. customto afford 0.100 g (50.2%) of I-46

Sources & evidence

ORD record
ord-37e7fbb1126e4149a9f33765eda42dab
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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