Sodium Carbonate Monohydrate → HCID 178476554, compound

HRID 51591

Reaction equation

Cl.I[C:3]1[C:11]2[C:10]([NH2:12])=[N:9][CH:8]=[N:7][C:6]=2[N:5]([C@H:13]2[CH2:18][CH2:17][C@H:16]([N:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)[CH2:15][CH2:14]2)[CH:4]=1.[O:26]([C:33]1[CH:40]=[CH:39][C:38](B2[O:45][C:44]([CH3:47])(C)C(C)(C)O2)=[CH:37][C:34]=1[CH:35]=[O:36])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[OH2:50].C(=O)([O-])[O-:52].[Na+].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:44]([OH:52])(=[O:45])[CH3:47].[C:27]([OH:26])(=[O:50])[CH3:28].[NH2:12][C:10]1[C:11]2[C:3]([C:38]3[CH:39]=[CH:40][C:33]([O:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[C:34]([CH:37]=3)[CH:35]=[O:36])=[CH:4][N:5]([C@H:13]3[CH2:18][CH2:17][C@H:16]([N:19]4[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]4)[CH2:15][CH2:14]3)[C:6]=2[N:7]=[CH:8][N:9]=1

Participants

Conditions

Temperature: 85 °C

Procedure

A mixture of trans-5-iodo-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride (750 mg, 1.63 mmol), 2-phenoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde (635 mg, 1.96 mmol), sodium carbonate monohydrate (490 mg, 3.92 mmol) and tetrakis(triphenylphosphine)palladium(0) (115 mg, 0.1 mmol) in ethylene glycol dimethyl ether (40 mL) and water (20 mL) was heated at 85° C. for 18 hours. The mixture was cooled, concentrated under reduced pressure then purified by preparative RP-HPLC then lyophilized to give trans-5-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-phenoxybenzaldehyde bisacetate (636 mg, 68%). A portion of this compound (75 mg, 0.132 mmol) was dissolved in ethanol (2 mL) and the treated with maleic acid (61 mg, 0.526 mmol) in ethanol (1 mL). The precipitate was collected by filtration and dried under reduced pressure: 1H NMR (DMSO-d6, 400 MHz) δ 10.41(s, 1H), 8.22(s, 1H), 7.88(s, 1H), 7.72(d, 1H), 7.60(s, 1H), 7.47(t, 2H), 7.24(m, 3H), 7.08(d, 1H), 6.62 (bs, 2H), 6.16(s, 6H), 4.61(m, 1H), 2.5-3.4(m, 9H), 2.69(s, 3H), 1.8-2.1 (m, 6H), 1.56 (m, 2H); MS MH+511.4; RP-HPLC (Hypersil HS, 5 μm, 100 A 4.6×250 mm; 5%-100% acetonitrile—0.05 M ammonium acetate over 25 min, 1 ml/min) tr 14.55 min.

Workup

temperatureThe mixture was cooled
concentrationconcentrated under reduced pressure
customthen purified by preparative RP-HPLC

Sources & evidence

ORD record: ord-13f9f053a72b4df1b254015f5422fb99
Source dataset: uspto-grants-2004_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06713474B2

Linked notes

Loading…