Diisopropylethylamine → HCID 77230602, compound

HRID 1520047Notes

Reaction equation

HRID 1520047 reaction equation
F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[C:28]([C:30]1[C:38]2[C:33](=[CH:34][CH:35]=[C:36]([C:39](O)=[O:40])[CH:37]=2)[N:32]([CH:42]2[CH2:47][CH2:46][CH2:45][CH2:44][O:43]2)[N:31]=1)#[CH:29].CCN(C(C)C)C(C)C.[BH4-].[Na+]>C1COCC1.CCOC(C)=O.CC(N(C)C)=O>[C:28]([C:30]1[C:38]2[C:33](=[CH:34][CH:35]=[C:36]([CH2:39][OH:40])[CH:37]=2)[N:32]([CH:42]2[CH2:47][CH2:46][CH2:45][CH2:44][O:43]2)[N:31]=1)#[CH:29]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 4311764Sodium borohydrideHCID 77230603HCID 77230603, compound

Product 1

HCID 77230602HCID 77230602, compoundYield 82.3%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

BOP (3.18 g; 7.19 mmol; 1.20 eq.) was added to a solution of 3-ethynyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylic acid (1.97 g; 5.97 mmol; 1.0 eq.) in DIEA (7 mL; 41.2 mmol; 6.9 eq.) and THF (350 mL). After 1 h, DMA (100 mL) was added in one portion followed by sodium borohydride (0.70 g; 18.5 mmol; 3.1 eq.). The reaction mixture was stirred at RT for 20 min, diluted with EtOAc and washed sequentially with 1 N HCl, NaHCO3 (sat) and NaCl (sat) solutions, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography on silica (EtOAc: n-heptane, gradient from 10:90 to 50:50) gave the title compound as a clear oil (1.26 g; 78.2%). 1H NMR (300 MHz, DMSO-d6) δ 7.75 (d, J=8.7 Hz, 1H), 7.65 (d, J=0.6 Hz, 1H), 7.43 (dd, J=8.7, 1.5 Hz, 1H), 5.87 (dd, J=9.5, 2.3 Hz, 1H), 5.29 (t, J=5.8 Hz, 1H), 4.62 (d, J=5.8 Hz, 2H), 4.58 (s, 1H), 3.93-3.82 (m, 1H), 3.80-3.68 (m, 1H), 2.44-2.27 (m, 1H), 2.08-1.91 (m, 2H), 1.83-1.64 (m, 1H), 1.63-1.51 (m, 2H). HPLC (max plot) 95.2%; Rt %2.78 min. UPLC/MS: (MS+) 257.2.

Workup

  1. washwashed sequentially with 1 N HCl, NaHCO3 (sat) and NaCl (sat) solutions
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by flash chromatography on silica (EtOAc: n-heptane, gradient from 10:90 to 50:50)

Sources & evidence

ORD record
ord-157aaab4cc8d440b9f6ea41d953db41a
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

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